HORMONES

What is a hormone?
A hormone is a chemical that is made by specialist cells, usually within an endocrine gland, and it is
released into the bloodstream to send a message to another part of the body. It is often referred to as
a ‘chemical messenger’. Hormones are found in all multicellular organisms and their role is to
provide an internal communication system between cells located in distant parts of the body.



In the human body, hormones are used for two types of communication. The first is for
communication between two endocrine glands, where one gland releases a hormone which
stimulates another target gland to change the levels of hormones that it is releasing. The second is
between an endocrine gland and a target organ, for example when the pancreas releases insulin
which causes muscle and fat cells to take up glucose from the bloodstream.



Since hormones are released into the bloodstream and can therefore be carried around the entire
body, they can perform both of these actions on many different targets. The complex interplay
between the glands, hormones and other target organs is referred to as the endocrine system.
Hormones affect many physiological activities including growth, metabolism, appetite, puberty and
fertility.

1. Adrenaline
2. Adrenocorticotropic hormone
3. Aldosterone
4. Androstenedione
5. Angiotensin
6. Anti-diuretic hormone
7. Anti-Müllerian hormone
8. Calcitonin
9. Cholecystokinin
10. Corticotrophin-releasing hormone
11. Cortisol
12. Dehydroepiandrosterone
13. Dihydrotestosterone
14. Erythropoietin
15. Follicle stimulating hormone
16. Gastrin
17. Ghrelin
18. Glucagon
19. Glucagon-like peptide 1
20. Glucose-dependent insulinotropic peptide
21. Gonadotrophin-releasing hormone
22. Growth hormone
23. Growth hormone-releasing hormone
24. Human chorionic gonadotrophin
25. Insulin
26. Kisspeptin
27. Leptin
28. Luteinising hormone
29. Melanocyte-stimulating hormone
30. Melatonin
31. Oestradiol
1
 HORMONES

32. Oestriol
33. Oestrone
34. Oxytocin
35. Parathyroid hormone
36. Peptide YY
37. Progesterone
38. Prolactin
39. Prostaglandins
40. Relaxin
41. Somatostatin
42. Testosterone
43. Thyroid stimulating hormone
44. Thyrotropin-releasing hormone
45. Thyroxine
46. Triiodothyronine
47. Vitamin D

2
 HORMONES

1. Adrenaline
Adrenaline is a hormone released from the adrenal glands and its major action, together with
noradrenaline, is to prepare the body for ‘fight or flight’.
Alternative names for adrenaline
Epinephrine

What is adrenaline?

Image of an eye showing a dilated or enlarged pupil–one of the effects of adrenaline released during
a ‘fight or flight’ response.

Adrenaline and noradrenline are two separate but related hormones and neurotransmitters. They are
produced in the centre (medulla) of the adrenal glands and in some neurons of the central nervous
system. They are released into the bloodstream and serve as chemical mediators, and also convey
the nerve impulses to various organs. Adrenaline has many different actions depending on the type
of cells it is acting upon. However, the overall effect of adrenaline is to prepare the body for the
‘fight or flight’ response in times of stress, i.e. for vigorous and/or sudden action. Key actions of
adrenaline include increasing the heart rate, increasing blood pressure, expanding the air passages
of the lungs, enlarging the pupil in the eye (see photo), redistributing blood to the muscles and
altering the body’s metabolism, so as to maximise blood glucose levels (primarily for the brain). A
closely related hormone, noradrenaline, is released mainly from the nerve endings of the
sympathetic nervous system (as well as in relatively small amounts from the adrenal medulla).
There is a continuous low level of activity of the sympathetic nervous system resulting in release of
noradrenaline into the circulation, but adrenaline release is only increased at times of acute stress.

How is adrenaline controlled?

Adrenaline is released mainly through the activation of nerves connected to the adrenal glands,
which trigger the secretion of adrenaline and thus increase the levels of adrenaline in the blood.
This process happens relatively quickly, within 2 to 3 minutes of the stressful event being

3
 HORMONES

encountered. When the stressful situation ends, the nerve impulses to the adrenal glands are
lowered, meaning that the adrenal glands stop producing adrenaline.

Stress also stimulates the release of adrenocorticotropic hormone from the pituitary gland, which
promotes the production of the steroid hormone cortisol from the cortex of the adrenal glands. This
steroid hormone is more important in altering the body’s metabolism (i.e. raising plasma glucose)
under conditions of longer-term, ongoing (chronic), rather than acute, stress.

What happens if I have too much adrenaline?

Overproduction of adrenaline is very common. Most people are exposed to stressful situations on
occasion and so most of us are familiar with the typical symptoms of adrenaline release, such as:
rapid heartbeat, high blood pressure, anxiety, weight loss, excessive sweating and palpitations.
However, this is a normal response of the body which is intended to help us respond to a stressful
situation; once the acute stress is over, the symptoms quickly disappear as adrenaline hyper-
secretion stops. Some people with obesity and untreated obstructive sleep apnea may be exposed to
high levels of noradrenaline/adrenaline each night as they struggle to breathe; this might play a role
in the development of high blood pressure in such people.

Very rarely, overproduction of adrenaline/noradrenaline may be caused by an adrenal tumour called

pheochromocytoma or a paraganglioma (if it is located outside the adrenal but along the nerves of
sympathetic nervous system that run through the chest and abdomen). Such tumours may run in
families as well. The symptoms can include the typical symptoms of adrenaline excess on an
intermittent basis but, in some cases, the symptoms can be quite mild so as to be barely noticeable.

What happens if I have too little adrenaline?

Suffering from too little adrenaline is very unusual, even if you have lost both adrenal glands
through disease or surgery. Since 90% of the body’s noradrenaline comes from the nervous system,
the loss of 10% via the adrenal glands is not really significant. ‘Adrenaline deficiency’ therefore
does not really show up as a medical disorder except perhaps in exceedingly rare and unusual
genetic catecholamine enzyme deficiencies.

4
 HORMONES

2. Adrenocorticotropic hormone
Adrenocorticotropic hormone is produced by the pituitary gland. Its key function is to stimulate the
production and release of cortisol from the cortex of the adrenal gland.
Alternative names for adrenocorticotropic hormone
ACTH; adrenocorticotrophin; corticotropin

What is adrenocorticotropic hormone?

Corticotrophin-releasing hormone from the hypothalamus acts on the pituitary (inset), which
secretes ACTH. ACTH travels to the adrenal glands via the bloodstream (arrow). Cortisol from the
adrenal then feeds back to the hypothalamus to shut down the cycle.

Adrenocorticotropic hormone is made in the corticotroph cells of the anterior pituitary gland. It is
secreted in several intermittent pulses during the day into the bloodstream and transported around
the body. Like cortisol, levels of adrenocorticotropic hormone are generally high in the morning
when we wake up and fall throughout the day. This is called a diurnal rhythm. Once
adrenocorticotropic hormone reaches the adrenal glands, it binds on to receptors causing the adrenal
glands to secrete more cortisol, resulting in higher levels of cortisol in the blood. It also increases
production of the chemical compounds that trigger an increase in other hormones such as adrenaline
and noradrenaline.

How is adrenocorticotropic hormone controlled?

5
 HORMONES

Secretion of adrenocorticotropic hormone is controlled by three inter-communicating regions of the

body, the hypothalamus, the pituitary gland and the adrenal glands. This is called the hypothalamic–
pituitary–adrenal axis. When adrenocorticotropic hormone levels in the blood are low, a group of
cells in the hypothalamus release a hormone called corticotrophin-releasing hormone which
stimulates the pituitary gland to secrete adrenocorticotropic hormone into the bloodstream. High
levels of adrenocorticotropic hormone are detected by the adrenal glands which stimulate the
secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to
slow down the release of corticotrophin-releasing hormone from the hypothalamus and
adrenocorticotropic hormone from the pituitary gland. As a result, the adrenocorticotropic hormone
levels start to fall. This is called a negative feedback loop.

Stress, both physical and psychological, also stimulates adrenocorticotropic hormone production
and hence increases cortisol levels.

What happens if I have too much adrenocorticotropic

hormone?
The effects of too much adrenocorticotropic hormone are mainly due to the increase in cortisol
levels which result. Higher than normal levels of adrenocorticotropic hormone may be due to:

Cushing’s disease – this is the most common cause of increased adrenocorticotropic hormone. It is
caused by a non-cancerous tumour called an adenoma located in the pituitary gland, which
produces excess amounts of adrenocorticotropic hormone. (Please note, Cushing’s disease is
just one of the numerous causes of Cushing’s syndrome).
A tumour, outside the pituitary gland, producing adrenocorticotropic hormone (also called ectopic
adrenocorticotropic hormone tumour).
Addison’s disease (although cortisol levels are low, adrenocorticotropic hormone levels are raised).
Congenital adrenal hyperplasia (a genetic disorder with inadequate production of cortisol,
aldosterone or both).
What happens if I have too little adrenocorticotropic
hormone?
Lower than normal levels of adrenocorticotropic hormone may be due to:

Cushing’s syndrome related to an adrenal tumour.

Cushing’s syndrome due to steroid medication.
Conditions affecting the pituitary gland, e.g. hypopituitarism.
Side-effect of pituitary surgery or radiation therapy.
Too little adrenocorticotropic hormone could lead to a poorly functioning adrenal gland due to
insufficient production of cortisol.

6
 HORMONES

3. Aldosterone
Aldosterone is a steroid hormone. Its main role is to regulate salt and water in the body, thus having
an effect on blood pressure.
What is aldosterone?
Aldosterone is a hormone produced in the outer section (cortex) of the adrenal glands, which sit
above the kidneys. It plays a central role in the regulation of blood pressure mainly by acting on
organs such as the kidney and the colon to increase the amount of salt (sodium) reabsorbed into the
bloodstream and to increase the amount of potassium excreted in the urine. Aldosterone also causes
water to be reabsorbed along with sodium; this increases blood volume and therefore blood
pressure.

How is aldosterone controlled?

Aldosterone is part of a group of linked hormones, which form the renin–angiotensin–aldosterone
system. Activation of this system occurs when there is decrease in blood flow to the kidneys
following loss of blood volume or a drop in blood pressure (e.g. due to a haemorrhage). Renin is an
enzyme that leads to a series of chemical reactions resulting in the production of angiotensin II,
which in turn stimulate aldosterone release. Aldosterone causes an increase in salt and water
reabsorption into the bloodstream from the kidney thereby increasing the blood volume, restoring
salt levels and blood pressure.

What happens if I have too much aldosterone?

The most common cause of high aldosterone levels is excess production, frequently from a small
benign adrenal tumour (primary hyperaldosteronism). The symptoms include high blood pressure,
low blood levels of potassium and an abnormal increase in blood volume.

What happens if I have too little aldosterone?

Low aldosterone levels are found in a rare condition called Addison’s disease. In Addison’s disease,
there is a general loss of adrenal function resulting in low blood pressure, lethargy and an increase
in potassium levels in the blood (see the article on Addison’s disease for further information).

7
 HORMONES

4. Androstenedione
Androstenedione is a steroid hormone that has weak, androgenic actions on the body itself.
However, it mainly acts as a stepping stone in the manufacture of testosterone and oestrogen within
the body.
Alternative names for androstenedione
Andro; andros; 4-Androstenedione. 17 ketotestosterone; 4-androsten-3,17-dione

What is androstenedione?
Androstenedione is described as a ‘pro-hormone’ because it has few effects itself. Instead, it is
important because of the ability of different parts of the body to convert it into the hormones,
testosterone and oestrogen, which exert many effects on the body.

In females, the outer part of the adrenal glands (known as the cortex) and the ovaries release
androstenedione into the bloodstream where it is converted to provide around half of all testosterone
and almost all of the body’s oestrone, a form of oestrogen. Although the testes produce large
amounts of androstenedione in males, they secrete little of this into the blood and, instead, rapidly
convert it into testosterone within the testes. The adrenal glands also produce androstenedione in
men, but this contribution is swamped by the testes’ overwhelming production of the other
androgenic hormone, testosterone.

How is androstenedione controlled?

Due to its secretion from a number of different glands and its often rapid conversion to other
hormones, the control of androstenedione within the body is very complex. However, two key parts
of the brain (the hypothalamus and pituitary gland) are known to be important in the control of
androstenedione secretion from the testes, ovaries and adrenal cortex. The release of
androstenedione by the adrenal cortex is thought to be related to the pituitary gland’s secretion of a
specialised hormone, adrenocorticotropic hormone. Precisely how adrenocorticotropic hormone and
other hormones control the adrenal gland’s production of androstenedione is, however, unclear. The
testes and ovaries are stimulated to release androstenedione by luteinising hormone and follicle
stimulating hormone. These are released from the anterior pituitary gland in response to a hormone
signal from the hypothalamus.

What happens if I have too much androstenedione?

The effects of too much androstenedione are likely to result from its conversion in the body to
oestrogen or testosterone.

In men, too much androstenedione may lead to an imbalance in oestrogen and testosterone
production, leading to changes such as breast development. Depending on the cause of the excess
androstenedione, other changes, such as the testes becoming smaller, might also occur.

8
 HORMONES

In women, excess body and facial hair growth (called hirsutism), stopping of periods
(amenorrhoea), worsening acne and changes to the genitalia may result from too much
androstenedione.

Although androstenedione is often abused by bodybuilders in an effort to build muscle bulk, a small
number of studies have suggested that its long-term use may actually decrease muscle strength. The
precise consequences of having too much androstenendione are, therefore, still unclear.

What happens if I have too little androstenedione?

Boys with too little androstenedione may fail to develop the sexual characteristics associated with
puberty, including pubic and body hair, growth of the sexual organs and deepening of the voice.
Similarly, girls may fail to start their periods and may not undergo many of the changes usually seen
in puberty. In addition, if a male foetus has too little androstenedione, he may be born with
abnormal genitalia. Too little androstenedione in later life would cause the same changes for both
men and women as too little testosterone and oestrogen.

9
 HORMONES

5. Angiotensin
Angiotensin is a protein hormone that causes blood vessels to become narrower. It helps to maintain
blood pressure and fluid balance in the body.
Alternative names for angiotensin
The different forms of angiotensin are denoted by Roman numerals, angiotensin I–IV. The
hormones and the way they are activated are often referred to together as the renin–angiotensin
system.

What is angiotensin?
The liver creates and releases a protein called angiotensinogen. This is then broken up by renin, an
enzyme produced in the kidney, to form angiotensin I. This form of the hormone is not known to
have any particular biological function in itself but, is an important precursor for angiotensin II. As
it passes in the bloodstream through the lungs and kidneys, it is further metabolised to produce
angiotensin II by the action of angiotensin-converting enzyme. Following binding to its receptor,
found in most tissues of the body, Angiotensin II has effects on:

blood vessels (vascular), to cause constriction (narrowing) of the blood vessels and hence to
increase blood pressure
nerves (neurological), to cause the sensation of thirst, desire for salt, and to encourage the release of
anti-diuretic hormone from the pituitary gland and noradrenaline from sympathetic nerves
adrenal glands, to stimulate aldosterone production, resulting in the body retaining sodium and
losing potassium from the kidneys
the kidneys, to increase sodium retention and to alter the way the kidneys filter blood. This
increases water reabsorption in the kidney to increase blood volume and blood pressure.
The overall effect of angiotensin II is to increase blood pressure, body water and sodium content.

How is angiotensin controlled?

An increase in renin production occurs if there is a decrease in sodium levels and a decrease in
blood pressure, which is sensed by the kidneys. In addition, low blood pressure can stimulate the
sympathetic nervous system to increase renin production, which results in increased conversion of
angiotensinogen to angiotensin I, and so the cylce continues. However, since angiotensin I has to be
converted to the more active angiotensin II hormone by the angiotensin-converting enzyme, before
it can function, this enables control over angiotensin metabolism. The renin–angiotensin system is
also activated by other hormones, including corticosteroids, oestrogen and thyroid hormones. On
the other hand, natriuretic peptides (produced in the heart and central nervous system) can impede
the renin–angiotensin system in order to increase sodium loss in the urine.

What happens if I have too much angiotensin?

Too much angiotensin II is a common problem resulting in excess fluid being retained by the body
and, ultimately, raised blood pressure. This often occurs in heart failure where angiotensin is also
thought to contribute to growth in the size of the heart. To combat these adverse effects, drugs such
as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used in the
10
 HORMONES

clinic, although these do have side effects and can lead to excessive retention of potassium
(hyperkalaemia).

What happens if I have too little angiotensin?

Control of plasma sodium and potassium concentrations, and the regulation of blood volume and
pressure, are all hormonal mechanisms that are impaired by low angiotensin levels. Absence of
angiotensin can be associated with retention of potassium, loss of sodium, decreased fluid retention
(increased urine output) and low blood pressure.

11
 HORMONES

6. Anti-diuretic hormone
Anti-diuretic hormone acts to maintain blood pressure, blood volume and tissue water content by
controlling the amount of water and hence the concentration of urine excreted by the kidney.
Alternative names for anti-diuretic hormone
Vasopressin; arginine vasopressin; AVP; ADH

What is anti-diuretic hormone?

Anti-diuretic hormone is made by special nerve cells found in an area at the base of the brain known
as the hypothalamus. The nerve cells transport the hormone down their nerve fibres (axons) to the
pituitary gland where the hormone is released into the bloodstream. Anti-diuretic hormone helps to
control blood pressure by acting on the kidneys and the blood vessels. Its most important role is to
conserve the fluid volume of your body by reducing the amount of water passed out in the urine. It
does this by allowing water in the urine to be taken back into the body in a specific area of the
kidney. Thus, more water returns to the bloodstream, urine concentration rises and water loss is
reduced. Higher concentrations of anti-diuretic hormone cause blood vessels to constrict (become
narrower) and this increases blood pressure. A deficiency of body fluid (dehydration) can only be
finally restored by increasing water intake.

How is anti-diuretic hormone controlled?

The release of anti-diuretic hormone from the pituitary gland into the bloodstream is controlled by a
number of factors. A decrease in blood volume or low blood pressure, which occurs during
dehydration or a haemorrhage, is detected by sensors (receptors) in the heart and large blood
vessels. These stimulate anti-diuretic hormone release. Secretion of anti-diuretic hormone also
occurs if the concentration of salts in the bloodstream increases, for example as a result of not
drinking enough water on a hot day. This is detected by special nerve cells in the hypothalamus
which simulate anti-diuretic hormone release from the pituitary. If the concentration of salts reaches
abnormally low levels, this condition is called hyponatraemia. Anti-diuretic hormone is also
released by thirst, nausea, vomiting and pain, and acts to keep up the volume of fluid in the
bloodstream at times of stress or injury. Alcohol prevents anti-diuretic hormone release, which
causes an increase in urine production and dehydration.

What happens if I have too much anti-diuretic hormone?

High levels of anti-diuretic hormone cause the kidneys to retain water in the body. There is a
condition called Syndrome of Inappropriate Anti-Diuretic Hormone secretion (SIADH; a type of
hyponatraemia) where excess anti-diuretic hormone is released when it is not needed (see the article
on hyponatraemia for more information). With this condition, excessive water retention dilutes the
blood, giving a characteristically low salt concentration. Excessive levels of anti-diuretic hormone
might be caused by drug side-effects and diseases of the lungs, chest wall, hypothalamus or
pituitary. Some tumours (particularly lung cancer), can produce anti-diuretic hormone.

What happens if I have too little anti-diuretic hormone?

12
 HORMONES

Low levels of anti-diuretic hormone will cause the kidneys to excrete too much water. Urine volume
will increase leading to dehydration and a fall in blood pressure. Low levels of anti-diuretic
hormone may indicate damage to the hypothalamus or pituitary gland, or primary polydipsia
(compulsive or excessive water drinking). In primary polydipsia, the low level of anti-diuretic
hormone represents an effort by the body to get rid of excess water. Diabetes insipidus is a
condition where you either make too little anti-diuretic hormone (usually due to a tumour, trauma or
inflammation of the pituitary or hypothalamus), or where the kidneys are insensitive to it. Diabetes
insipidus is associated with increased thirst and urine production.

13
 HORMONES

7. Anti-Müllerian hormone
Anti-Müllerian hormone is important in the development of the reproductive tract in a male foetus
and is also produced by the testes and ovaries.
Alternative names for anti-Müllerian hormone
AMH; Müllerian inhibiting factor; MIF; Müllerian-inhibiting hormone; MIH; Müllerian-inhibiting
substance; MIS

What is anti-Müllerian hormone?

About eight weeks after conception the human foetus has two sets of ducts, one of which can
develop into the male reproductive tract and the other into the female reproductive tract. If the
foetus is genetically male (XY chromosomes) then the embryonic testes will produce anti-Müllerian
hormone. This causes the Müllerian (female) ducts to shut down and the male (Woolfian) ducts to
survive – hence the term anti-Müllerian hormone. The Woolfian ducts are then free to develop into
different parts of the testes: the epididymus, the vas deferens and the seminal vesicles. In a female
foetus (XX chromosomes) the Woolfian ducts shut down and the Müllerian ducts develop into the
fallopian tubes, uterus (womb), cervix and the upper part of the vagina. Anti-Müllerian hormone
may also have a role in regulating sex steroid production in puberty and in the adult ovaries and
testes. In the ovaries, anti-Müllerian hormone is important in the early stages of development of the
follicles. These are eggs surrounded by one or more layers of cells.

How is anti-Müllerian hormone controlled?

It is not currently known how the production of anti-Müllerian hormone is controlled.

What happens if I have too much or too little anti-Müllerian

hormone?
When the male foetus does not produce enough anti-Müllerian hormone, the Müllerian ducts do not
shut down and this leads to persistent Müllerian duct syndrome. Patients with this syndrome will
have a male appearance but they usually have undescended testes (cryptchordism) and low or
absent sperm count due to abnormal development of the Woolfian duct. This leads to malformation
of the vas deferens and epididymus. This condition is rare.

Measuring levels of anti-Müllerian hormone provides a way of estimating ovarian reserve in

women, in other words, how responsive the ovaries are to stimulation by the pituitary gland (see
article on follicle stimulating hormone). Consequently, anti-Müllerian hormone levels are routinely
used to predict how well a woman is likely to respond to in vitro fertilisation (IVF) fertility
treatment, and what doses of hormones should be used during IVF.

In women anti-Müllerian hormone levels peak around puberty and remain relatively constant until
after the menopause, when no follicles remain, and levels of anti-Müllerian hormone become low.
Some studies suggest that levels of anti-Müllerian hormone may be lower than normal in women
who undergo premature ovarian failure. However, anti-Müllerian hormone results need to be
interpreted with caution since many other factors can affect an individual’s fertility.
14
 HORMONES

High levels of anti-Müllerian hormone may be associated with polycystic ovary syndrome.
However, measuring anti-Müllerian hormone can be misleading and does not give a definitive
diagnosis of either premature ovarian failure or polycystic ovary syndrome. It is important that any
test to measure anti-Müllerian hormone levels is carried out by a qualified medical professional.

15
 HORMONES

8. Calcitonin
Calcitonin is a hormone that is produced and released by the C-cells of the thyroid gland. Its
biological function in humans is to have a relatively minor role in calcium balance.
Alternative names for calcitonin
CT; thyrocalcitonin

What is calcitonin?
Calcitonin is a hormone that is produced in humans by the parafollicular cells (commonly known as
C-cells) of the thyroid gland. Calcitonin is involved in helping to regulate levels of calcium and
phosphate in the blood, opposing the action of parathyroid hormone. This means that it acts to
reduce calcium levels in the blood. However, the importance of this role in humans is unclear, as
patients who have very low or very high levels of calcitonin show no adverse effects.

Calcitonin reduces calcium levels in the blood by two main mechanisms:

1. It inhibits the activity of osteoclasts, which are the cells responsible for breaking down bone.
When bone is broken down, the calcium contained in the bone is released into the
bloodstream. Therefore, the inhibition of the osteoclasts by calcitonin directly reduces the
amount of calcium released into the blood. However, this inhibition has been shown to be
short-lived.
2. It can also decrease the resorption of calcium in the kidneys, again leading to lower blood
calcium levels.
Manufactured forms of calcitonin have, in the past, been given to treat Paget’s disease of bone and
sometimes hypercalcaemia and bone pain. However, with the introduction of newer drugs, such as
bisphosphonates, their use is now very limited.

How is calcitonin controlled?

The secretion of both calcitonin and parathyroid hormone is determined by the level of calcium in
the blood. When levels of calcium in the blood increase, calcitonin is secreted in higher quantities.
When levels of calcium in the blood decrease, this causes the amount of calcitonin secreted to
decrease too.

The secretion of calcitonin is also inhibited by the hormone somatostatin, which can also be
released by the C-cells in the thyroid gland.

What happens if I have too much calcitonin?

There does not seem to be any direct deleterious effect on the body as a result of having too much
calcitonin.

Medullary thyroid cancer is a rare type of cancer that arises from the C-cells in the thyroid gland
that secrete calcitonin. It is sometimes associated with multiple endocrine neoplasia type 2a and
multiple endocrine neoplasia type 2b. Patients with medullary thyroid cancer have high calcitonin

16
 HORMONES

levels in their bloodstream. However, it is important to note that these high calcitonin levels are a
consequence of this condition, not a direct causal factor.

What happens if I have too little calcitonin?

There does not seem to be any clinical effect on the body as a result of having too little calcitonin.
Patients who have had their thyroid gland removed, and have undetectable levels of calcitonin in
their blood, show no adverse symptoms or signs as a result of this.

17
 HORMONES

9. Cholecystokinin
Cholecystokinin is a gut hormone released after a meal, which helps digestion and reduces appetite.
Alternative names for cholecystokinin
Cholecystokinin used to be known as pancreozymin due to its actions on the pancreas but now it is
commonly abbreviated to CCK; CCK-PZ

What is cholecystokinin?
Cholecystokinin is produced by I-cells in the lining of the duodenum and is also released by some
neurons in the brain. It acts on two types of receptors found throughout the gut and central nervous
system.

The most recognised functions of this hormone are in digestion and appetite. It improves digestion
by slowing down the emptying of food from the stomach and stimulating the production of bile in
the liver as well as its release from the gall bladder. Bile acts like a detergent making the fat droplets
smaller so that enzymes can break it down more easily. Cholecystokinin also increases the release
of fluid and enzymes from the pancreas to break down fats, proteins and carbohydrates.

Cholecystokinin seems to be involved with appetite by increasing the sensation of fullness in the
short-term, that is, during a meal rather than between meals. It may do this by affecting appetite
centres in the brain as well as delaying emptying of the stomach. However, more research is needed
to confirm this finding.

There is also evidence to suggest that cholecystokinin may have a role in anxiety and panic
disorders. This is an effect of cholecystokinin released in the brain, not an effect of secretion from
other parts of the body.

How is cholecystokinin controlled?

Fat and protein in the stomach cause the release of cholecystokinin. Increased blood levels of
cholecystokinin can be found 15 minutes after a meal has begun and levels remain raised for three
hours afterwards. The release of cholecystokinin is blocked by the hormone somatostatin and by
bile acids in the small intestine.

What happens if I have too much cholecystokinin?

There are no known cases of too much cholecystokinin. However, weight loss drugs are currently
under development that copy the appetite-reducing actions of cholecystokinin.

What happens if I have too little cholecystokinin?

Some research has been carried out to examine blood levels of cholecystokinin when people are
fasting or just after they have eaten. There appears to be evidence of less than average
cholecystokinin in very obese people, unlike the levels in obese and slim people. This low level of
cholecystokinin may contribute to reduced feelings of fullness and difficulty in losing weight in
18
 HORMONES

very obese people. However, more research is needed to confirm this finding. Variations in the
cholecystokinin gene itself have been associated with obesity, with an increased risk of 60% if
people carry the slightly different form (variant) called cholecystokinin H3. How this happens is
currently unclear.

19
 HORMONES

10. Corticotrophin-releasing hormone

Corticotrophin-releasing hormone is the main element that drives the body’s response to stress. It is
also present in diseases that cause inflammation. Too much or too little corticotrophin-releasing
hormone can have a range of negative effects.
Alternative names for corticotrophin-releasing hormone
Corticotropin-releasing hormone; corticotrophin-releasing factor; corticotropin-releasing factor;
corticoliberin; CRH; CRF

What is corticotrophin-releasing hormone?

Corticotrophin-releasing hormone is secreted by the paraventricular nucleus of the hypothalamus
which, among other functions, releases hormones. Corticotrophin-releasing hormone has several
important actions. Its main role in the body is as the central driver of the stress hormone system,
known as the hypothalamic–pituitary–adrenal axis. Corticotrophin-releasing hormone is given this
name because it causes release of adrenocorticotropic hormone from the pituitary gland.
Adrenocorticotropic hormone in turn travels in the bloodstream to the adrenal glands, where it
causes the secretion of the stress hormone cortisol.

Corticotrophin-releasing hormone also acts on many other areas within the brain where it
suppresses appetite, increases anxiety, and improves memory and selective attention. Together,
these effects co-ordinate behaviour to develop and fine tune the body’s response to a stressful
experience.

Corticotrophin-releasing hormone is also produced throughout pregnancy in increasing amounts by

the foetus and the placenta, with the effects of increasing cortisol. Ultimately, it is the high levels of
corticotrophin-releasing hormone that, along with other hormones, are thought to start labour.

Finally, in smaller quantities, corticotrophin-releasing hormone is also made by certain white blood
cells, where it stimulates swelling or tenderness known as inflammation, particularly of the gut.

How is corticotrophin-releasing hormone controlled?

Corticotrophin-releasing hormone secretion is stimulated by nervous activity within the brain. It
follows a natural 24 hour rhythm in non-stressed circumstances, where it is highest at around 8 a.m.
and lowest overnight. However, corticotrophin-releasing hormone can also be increased above the
normal daily levels by a stressful experience, infection or even exercise. An increase in
corticotrophin-releasing hormone leads to higher levels of the stress hormone cortisol which
mobilises energy resources needed for dealing with the cause of the stress. High levels of stress
hormones over a long period can have negative effects on the body. Because of this, cortisol blocks
the continued release of corticotrophin-releasing hormone and switches off the hypothalamus–
pituitary–adrenal axis, which is known as a negative feedback loop.

Some effects of corticotrophin-releasing hormone in the brain can also be blocked by leptin, a
hormone produced by fat tissue. This may be partly why corticotrophin-releasing hormone can
control appetite.

20
 HORMONES

What happens if I have too much corticotrophin-releasing

hormone?
Abnormally high corticotrophin-releasing hormone levels are connected with a variety of diseases.
Because it stimulates anxiety and suppresses appetite, too much corticotrophin-releasing hormone is
suspected of causing nervous problems such as clinical depression, anxiety, sleep disturbances and
anorexia nervosa.

In addition, high levels of corticotrophin-releasing hormone may also make certain inflammatory
problems worse, including rheumatoid arthritis, psoriasis, ulcerative colitis and Crohn’s disease.
Initially this might seem unexpected because raised levels of corticotrophin-releasing hormone in
the brain can lead to increased glucocorticoids production, and glucocorticoids have an anti-
inflammatory effect. However, research has revealed that when high levels of corticotrophin-
releasing hormone occur in tissues outside the brain, they can actually have a powerful
inflammatory action. Increased corticotrophin-releasing hormone levels within the joints, skin or
gut can therefore make these inflammatory conditions worse or even play a role in their
development.

What happens if I have too little corticotrophin-releasing

hormone?
Research has shown that people with Alzheimer’s disease have particularly low corticotrophin-
releasing hormone levels. Some scientists also suspect that a lack of corticotrophin-releasing
hormone might cause chronic fatigue syndrome, sometimes called Myalgic encephalomyelitis,
where sufferers have problems with sleep, memory and concentration. However, further research is
needed into both these topics before this can be confirmed.

During pregnancy, low corticotrophin-releasing hormone production by the foetus or the placenta
can result in miscarriage.

21
 HORMONES

11. Cortisol
Cortisol is a steroid hormone that regulates a wide range of processes throughout the body,
including metabolism and the immune response. It also has a very important role in helping the
body respond to stress.
Alternative names for cortisol
Hydrocortisone

What is cortisol?
Cortisol is a steroid hormone, one of the glucocorticoids, made in the cortex of the adrenal glands
and then released into the blood, which transports it all round the body. Almost every cell contains
receptors for cortisol and so cortisol can have lots of different actions depending on which sort of
cells it is acting upon. These effects include controlling the body’s blood sugar levels and thus
regulating metabolism, acting as an anti-inflammatory, influencing memory formation, controlling
salt and water balance, influencing blood pressure and helping development of the foetus. In many
species cortisol is also responsible for triggering the processes involved in giving birth.

A similar version of this hormone, known as corticosterone, is produced by rodents, birds and
reptiles.

How is cortisol controlled?

Blood levels of cortisol vary dramatically, but generally are high in the morning when we wake up,
and then fall throughout the day. This is called a diurnal rhythm. In people that work at night, this
pattern is reversed, so the timing of cortisol release is clearly linked to daily activity patterns. In
addition, in response to stress, extra cortisol is released to help the body to respond appropriately.

The secretion of cortisol is mainly controlled by three inter-communicating regions of the body, the
hypothalamus in the brain, the pituitary gland and the adrenal gland. This is called the
hypothalamic–pituitary–adrenal axis. When cortisol levels in the blood are low, a group of cells in a
region of the brain called the hypothalamus releases corticotrophin-releasing hormone, which
causes the pituitary gland to secrete another hormone, adrenocorticotropic hormone, into the
bloodstream. High levels of adrenocorticotropic hormone are detected in the adrenal glands and
stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise,
they start to block the release of corticotrophin-releasing hormone from the hypothalamus and
adrenocorticotropic hormone from the pituitary. As a result the adrenocorticotropic hormone levels
start to drop, which then leads to a drop in cortisol levels. This is called a negative feedback loop.

What happens if I have too much cortisol?

Too much cortisol over a prolonged period of time can lead to a condition called Cushing’s
syndrome. This can be caused by a wide range of factors, such as a tumour that produces
adrenocorticotropic hormone (and therefore increases cortisol secretion), or taking certain types of
drugs. The symptoms include:

22
 HORMONES

rapid weight gain mainly in the face, chest and abdomen contrasted with slender arms and legs
a flushed and round face
high blood pressure
osteoporosis
skin changes (bruises and purple stretch marks)
muscle weakness
mood swings, which show as anxiety, depression or irritability
increased thirst and frequency of urination.
High cortisol levels over a prolonged time can also cause lack of sex drive and, in women, periods
can become irregular, less frequent or stop altogether (amenorrhoea).

In addition, there has been a long-standing association between raised or impaired regulation of
cortisol levels and a number of psychiatric conditions such as anxiety and depression. However, the
significance of this is not yet clearly understood.

What happens if I have too little cortisol?

Too little cortisol can be due to a condition called Addison’s disease. It has a number of causes, all
rare, including damage to the adrenal glands by autoimmune disease. The onset of symptoms is
often very gradual. Symptoms may include fatigue, dizziness (especially upon standing), weight
loss, muscle weakness, mood changes and the darkening of regions of the skin. Urgent assessment
by a specialist hormone doctor called an endocrinologist is required when a diagnosis of Cushing’s
syndrome or Addison’s disease is suspected.

23
 HORMONES

12. Dehydroepiandrosterone
Dehydroepiandrosterone is an important precursor hormone, and is the most abundant circulating
steroid present in the human body. It has little biological effect on its own but has powerful effects
when converted into other hormones such as sex steroids.
Alternative names for dehydroepiandrosterone
DHEA; 3-beta-Hydroxy-5-androsten-17-one; synthetic versions – prastera, prasterone, fidelin and
fluasterone

What is dehydroepiandrosterone?
Dehydroepiandrosterone is a precursor hormone, which means it has little biological effect on its
own, but has powerful effects when converted into other hormones such as testosterone and
oestradiol. Dehydroepiandrosterone is produced from cholesterol mainly by the outer layer of the
adrenal glands, known as the adrenal cortex, although it is also made by the testes and ovaries in
small amounts. It circulates in the blood, mainly attached to sulphur as dehydroepiandrosterone
sulphate, which prevents the hormone being broken down. In women, dehydroepiandrosterone is an
important source of oestrogens in the body – it provides about 75% of oestrogens before the
menopause, and 100% of oestrogens in the body after menopause.

Dehydroepiandrosterone production increases from around nine or ten years of age, peaks during
the 20s and gradually decreases into old age. Dehydroepiandrosterone is also produced in small
amounts by the brain, although its precise role there is not clear.

How is dehydroepiandrosterone controlled?

Dehydroepiandrosterone production is controlled by the brain in a negative feedback loop. This
means that when dehydroepiandrosterone levels in the body fall, the system is ‘switched on’ and, as
levels rise, it ‘switches off’ again.

The system is ‘switched on’ by corticotrophin-releasing hormone being produced by the

hypothalamus. This travels to the anterior pituitary gland and causes it to release
adrenocorticotropic hormone into the bloodstream. Both of these hormones cause the adrenal glands
to produce dehydroepiandrosterone. When dehydroepiandrosterone levels rise, the body shuts off
production by stopping corticotrophin-releasing hormone and adrenocorticotropic hormone.

What happens if I have too much dehydroepiandrosterone?

Women with polycystic ovary syndrome and hirsutism and children with congenital adrenal
hyperplasia have higher levels of dehydroepiandrosterone/dehydroepiandrosterone sulphate. In
addition, levels may be raised in individuals with cancer of the adrenal glands (adrenal carcinoma).

High levels of dehydroepiandrosterone have also been linked to reducing the risk of depression,
cardiovascular disease and even death in some studies. Some experts have suggested
dehydroepiandrosterone supplements might overcome age-related decline (a so-called ‘elixir of
youth’) but this is not supported by current evidence.

24
 HORMONES

Some athletes and bodybuilders also take dehydroepiandrosterone (an anabolic steroid) to increase
muscle mass and strength. Serious side-effects from taking manufactured dehydroepiandrosterone
have been reported and it is banned by the World Anti-Doping Agency. However, exercise and
calorie-restriction have been shown to increase natural dehydroepiandrosterone levels in the body
and may lead to longer life.

Since 2000, dehydroepiandrosterone supplementation in combination with gonadotropins has been

used in reproductive medicine as a way to treat female infertility.

What happens if I have too little dehydroepiandrosterone?

Low levels of dehydroepiandrosterone have been linked with shorter lifespan in men but not
women. However, the reason for this is not fully understood. Decreased dehydroepiandrosterone
levels are associated with increased risk of cardiovascular disease in men with type 2 diabetes
mellitus and may also cause a shorter lifespan, although further research is needed to confirm this.

In women, low levels of dehydroepiandrosterone are associated with low libido, reduced bone
mineral density and osteoporosis. However, supplementation with commercially available
dehydroepiandrosterone is not recommended as there is concern about numerous possible side-
effects.

25
 HORMONES

13. Dihydrotestosterone
Dihydrotestosterone, a hormone with powerful androgenic actions, causes the body to mature
during puberty and is responsible for many of the physical characteristics associated with adult
males.
Alternative names for dihydrotestosterone
DH; 5α-dihydrotestosterone

What is dihydrotestosterone?
Dihydrotestosterone is a hormone that stimulates the development of male characteristics (an
androgen). It is made through conversion of the more commonly known androgen, testosterone.
Almost 10% of the testosterone produced by an adult each day is converted to dihydrotestosterone,
by the testes and prostate (in men), the ovaries (in women), the skin and other parts of the body.
This figure is much lower before puberty however, and it is thought that the increased
dihydrotestosterone production may be responsible for the start of puberty in boys, causing
development of the genitals (penis, testes and scrotum) and growth of pubic and body hair. This
hormone also causes the prostate to grow and is thought to combine with testosterone causing the
expression of male sexual behaviour. Dihydrotestosterone is many times more potent than
testosterone, and many of the effects that testosterone has in the body only happen after it is
converted to dihydrotestosterone.

Less is known about the importance of dihydrotestosterone in women, but it is known to cause
much of the body and pubic hair growth seen in girls after puberty and may help to determine the
age at which girls begin puberty.

How is dihydrotestosterone controlled?

The amount of dihydrotestosterone present in the body from day to day depends on the amount of
testosterone present. When levels of testosterone increase, more of it is converted to
dihydrotestosterone and so levels of dihydrotestosterone therefore also increase as a result.

Control of dihydrotestosterone levels in the body is therefore achieved through control of

testosterone production, which is controlled by the hypothalamus and the pituitary gland. In
response to decreasing levels of testosterone (and therefore reduced amounts of
dihydrotestosterone), the hypothalamus releases gonadotrophin-releasing hormone, which travels to
the pituitary gland, stimulating it to produce and release luteinising hormone into the bloodstream.
Luteinising hormone in the blood then travels to the Leydig cells in the testes in men (or ovaries in
women) and stimulates them to produce more testosterone. As testosterone in the blood increases,
more of it is also converted to dihydrotestosterone, resulting in higher levels of dihydrotestosterone
as well.

As blood levels of testosterone and dihydrotestosterone increase, this feeds back to suppress the
production of gonadotrophin-releasing hormone from the hypothalamus which, in turn, suppresses
production of luteinising hormone by the pituitary gland. Levels of testosterone (and thus
dihydrotestosterone) begin to fall as a result, so negative feedback decreases and the hypothalamus
resumes secretion of gonadotrophin-releasing hormone.
26
 HORMONES

What happens if I have too much dihydrotestosterone?

Too much dihydrotestosterone, often resulting from excess testosterone production, has variable
effects on men and women. It is unlikely that levels of dihydrotestosterone will be raised before the
start of puberty. It is also unlikely that adult men with too much dihydrotestosterone would undergo
recognisable changes. Women with too much dihydrotestosterone may develop increased body,
facial and pubic hair growth (called hirsutism), stopping of menstrual periods (amenorrhoea) and
increased acne. Abnormal changes to the genitalia may also occur in women with too much
dihydrotestosterone.

What happens if I have too little dihydrotestosterone?

Dihydrotestosterone is thought to have fewer effects in women and, as a result, it is believed they
are relatively unaffected by having too little dihydrotestosterone. It is possible, however, that the
start of puberty may be delayed in girls with too little dihydrotestosterone and the amount of pubic
and body hair present in adult females may also be reduced.

In contrast, low levels of dihydrotestosterone in men can have dramatic effects. If there is too little
dihydrotestosterone whilst male foetuses are still in the womb, for example, they may not be
‘masculinised’ and their genitalia may seem similar to that seen in girls of the same age. Later, boys
with too little dihydrotestosterone may undergo some of the changes usually seen in puberty (such
as muscle growth and production of sperm) but will not develop normal body hair growth and
genital development.

27
 HORMONES

14. Erythropoietin
Erythropoietin is a hormone, produced mainly in the kidneys, which stimulates the production and
maintenance of red blood cells.
Alternative names for erythropoietin
Erythropoietin is commonly referred to as EPO. It is also called haematopoietin or haemopoietin,
but these names are rarely used today.

What is erythropoietin?

Erythropoeitin testing in sport. Blood sample being tested for the presence of the performance-
enhancing hormone erythropoeitin.

Erythropoietin is a hormone that is produced predominantly by specialised cells in the kidney. Once
it is made, it acts on red blood cells to protect them against destruction. At the same time it
stimulates stem cells of the bone marrow to increase the production of red blood cells.

How is erythropoietin controlled?

Althought the precise mechanisms that control the production of erythropoietin are poorly
understood, it is well known that specialised cells in the kidney are capable of detecting and
responding to low levels of oxygen through increased production of erythropoietin. When there is
sufficient oxygen in the blood circulation, the production of erythropoietin is reduced, but when
oxygen levels go down, the production of erythropoietin goes up. This is adaptive because it
facilitates the production of more red blood cells to transport more oxygen around the body, thus
28
 HORMONES

raising oxygen levels in the tissues. For example, erythropoietin production will go up when
moving to a high altitude. This is because the air pressure is lower, the pressure of oxygen is lower
and so less oxygen is taken up by the blood therefore stimulating erythropoietin production. In low
oxygen states people risk developing hypoxia–oxygen deprivation. Hypoxia can also occur when
there is poor ventilation of the lungs such as occurs in emphysema and in cardiovascular disease.
The production of erythropoietin decreases in kidney failure and various chronic diseases such as
AIDS, certain cancers and chronic inflammatory diseases like rheumatoid arthritis.

What happens if I have too much erythropoietin?

Excess erythropoietin results from chronic low oxygen levels or from rare tumours that produce
high levels of erythropoietin. It causes a condition known as polycythaemia which is a high red
blood cell count. In many people, polycythaemia does not cause any symptoms. However, there are
some general and non-specific symptoms including weakness, fatigue, headache, itching, joint pain
and dizziness.

What happens if I have too little erythropoietin?

If you have too little erythropoietin, which is usually caused by chronic kidney disease, there will be
fewer red blood cells and you will have anaemia. Erythropoietin has been made synthetically for the
treatment of anaemia that results from chronic kidney failure. It is also given to patients with some
rarer types of cancer.

Some professional athletes have used this type of erythropoietin (known as blood doping) to
improve their performance, particularly to increase endurance. Artificially increasing your
erythropoietin levels produces more haemoglobin and red blood cells and therefore improves the
amount of oxygen that can be delivered to tissues, particularly muscles. This can improve
performance, although this type of doping practice is banned by most professional sport
committees.

29
 HORMONES

15. Follicle stimulating hormone

Follicle stimulating hormone is produced by the pituitary gland. It regulates the functions of both
the ovaries and testes. Lack or insufficiency of it can cause infertility or subfertility both in men and
women.
Alternative names for follicle stimulating hormone
FSH; follitropin (pharmaceutical preparations)

What is follicle stimulating hormone?

Follicle stimulating hormone is one of the gonadotrophic hormones, the other being luteinising
hormone. Both are released by the pituitary gland into the bloodstream. Follicle stimulating
hormone is one of the hormones essential to pubertal development and the function of women’s
ovaries and men’s testes. In women, this hormone stimulates the growth of ovarian follicles in the
ovary before the release of an egg from one follicle at ovulation. It also increases oestradiol
production. In men, follicle stimulating hormone acts on the Sertoli cells of the testes to stimulate
sperm production (spermatogenesis).

How is follicle stimulating hormone controlled?

The production and release of follicle stimulating hormone is regulated by the levels of a number of
circulating hormones released by the ovaries and testes. This system is called the hypothalamic–
pituitary–gonadal axis. Gonadotrophin-releasing hormone is released from the hypothalamus and
binds to receptors in the anterior pituitary gland to stimulate both the synthesis and release of
follicle stimulating hormone and luteinising hormone. The released follicle stimulating hormone is
carried in the bloodstream where it binds to receptors in the testes and ovaries. Using this
mechanism follicle stimulating hormone, along with luteinising hormone, can control the functions
of the testes and ovaries.

In women, when hormone levels fall towards the end of the menstrual cycle, this is sensed by nerve
cells in the hypothalamus. These cells produce more gonadotrophin-releasing hormone, which in
turn stimulates the pituitary gland to produce more follicle stimulating hormone and luteinising
hormone, and release these into the bloodstream. The rise in follicle stimulating hormone stimulates
the growth of the follicle in the ovary. With this growth, the cells of the follicles produce increasing
amounts of oestradiol and inhibin. In turn, the production of these hormones is sensed by the
hypothalamus and pituitary gland and less gonadotrophin-releasing hormone and follicle
stimulating hormone will be released. However, as the follicle matures, and more and more
oestrogen is produced from the follicles, it simulates a surge in luteinising hormone and follicle
stimulating hormone, which stimulates the release of an egg from a mature follicle – ovulation.

Thus, during each menstrual cycle, there is a rise in follicle stimulating hormone secretion in the
first half of the cycle that stimulates follicular growth in the ovary. After ovulation the ruptured
follicle forms a corpus luteum that produces high levels of progesterone. This inhibits the release of
follicle stimulating hormone. Towards the end of the cycle the corpus luteum breaks down,
progesterone production decreases and the next menstrual cycle begins when follicle stimulating
hormone starts to rise again.

30
 HORMONES

In men, the production of follicle stimulating hormone is regulated by the circulating levels of
testosterone and inhibin, both produced by the testes. Follicle stimulating hormone regulates
testosterone levels and when these rise they are sensed by nerve cells in the hypothalamus so that
gonadotrophin-releasing hormone secretion and consequently follicle stimulating hormone is
decreased. The opposite occurs when testosterone levels decrease. This is known as a ‘negative
feedback’ control so that the production of testosterone remains steady. The production of inhibin is
also controlled in a similar way but this is sensed by cells in the anterior pituitary gland rather than
the hypothalamus.

What happens if I have too much follicle stimulating

hormone?
Most often, raised levels of follicle stimulating hormone are a sign of malfunction in the ovary or
testis. If the gonads fail to create enough oestrogen, testosterone and/or inhibin, the correct feedback
control of follicle stimulating hormone production from the pituitary gland is lost and the levels of
both follicle stimulating hormone and luteinising hormone will rise. This condition is called
hypergonadotrophic-hypogonadism, and is associated with primary ovarian failure or testicular
failure. This is seen in conditions such as Kallmann’s syndrome in men and Turner syndrome in
women.

In women, follicle stimulating hormone levels also start to rise naturally in women around the
menopausal period, reflecting a reduction in function of the ovaries and decline of oestrogen and
progesterone production.

There are very rare pituitary conditions that can raise the levels of follicle stimulating hormone in
the bloodstream. This overwhelms the normal negative feedback loop and can cause ovarian
hyperstimulation syndrome in women. Symptoms of this include enlarging of the ovaries and a
potentially dangerous accumulation of fluid in the abdomen (triggered by the rise in ovarian steroid
output), which leads to pain in the pelvic area.

What happens if I have too little follicle stimulating hormone?

In women, a lack of follicle stimulating hormone leads to incomplete development at puberty and
poor ovarian function (primary ovarian failure). In this situation ovarian follicles do not grow
properly and do not release an egg, thus leading to infertility. Since levels of follicle stimulating
hormone in the bloodstream are low, this condition is called hypogonadotrophic-hypogonadism.

Sufficient follicle stimulating hormone action is also needed for proper sperm production. In the
case of complete absence of follicle stimulating hormone in men, lack of puberty and infertility due
to lack of sperm (azoospermia) can occur. Partial follicle stimulating hormone deficiency in men
can cause delayed puberty and limited sperm production (oligozoospermia), but fathering a child
may still be possible. If the loss of follicle stimulating hormone occurs after puberty, there will be a
similar loss of fertility.

31
 HORMONES

16. Gastrin
Gastrin is a hormone produced by the stomach, which stimulates the release of gastric acid.
What is gastrin?
Gastrin is a hormone that is produced by ‘G’ cells in the lining of the stomach and upper small
intestine. During a meal, gastrin stimulates the stomach to release gastric acid. This allows the
stomach to break down proteins swallowed as food and absorb certain vitamins. It also acts as a
disinfectant and kills most of the bacteria that enter the stomach with food, minimising the risk of
infection within the gut.

Gastrin also stimulates growth of the stomach lining and increases the muscle contractions of the
gut to aid digestion.

How is gastrin controlled?

Before a meal, the anticipation of eating stimulates nerves within the brain which signal to the
stomach and stimulate the release of gastrin. Gastrin release is also stimulated by the stretch of the
stomach walls during a meal, the presence of certain foods (particularly proteins) within the
stomach cavity and an increase in the pH levels of the stomach (i.e. the stomach becoming less
acidic).

The production and release of gastrin is slowed by the hormone somatostatin, which is released
when the stomach empties at the end of a meal and when the pH of the stomach becomes too acidic
(pH less than 3).

What happens if I have too much gastrin?

An excess of gastrin can occur due to a gastrin-secreting tumour (gastrinoma, also known as
Zollinger-Ellison syndrome). In gastrinomas, high levels of gastrin moving around the gut stimulate
acid release, leading to stomach and small intestine ulcers that may burst. High levels of stomach
acid can also cause diarrhoea because the lining of the small intestine becomes damaged.

High levels of circulating gastrin can also occur when the pH of the stomach is high (i.e. not acidic
enough), for example, in pernicious anaemia or atrophic gastritis when the stomach lining is
damaged and unable to produce and release acid, and during treatment with antacid drugs.

As gastrin also stimulates growth of the stomach lining, it is thought that high gastrin levels may
play a role in the development of certain cancers of the digestive tract. However, this has not been
proven.

What happens if I have too little gastrin?

It is rare to have too little gastrin. However, low levels of gastric acid may increase the risk of
infection within the gut and may limit the ability of the stomach to absorb nutrients.

32
 HORMONES

17. Ghrelin
Ghrelin is produced by the stomach. Among its numerous functions, ghrelin increases appetite and
stimulates the release of growth hormone.
What is ghrelin?
Ghrelin is a hormone that is produced and released mainly by the stomach with small amounts also
released by the small intestine, pancreas and brain.

Ghrelin has numerous functions. It is termed the ‘hunger hormone’ because it stimulates appetite,
increases food intake and promotes fat storage. When administered to humans, ghrelin increases
food intake by up to 30% by circulating in the bloodstream at the hypothalamus, an area of the brain
crucial in the control of appetite. Recently, ghrelin has also been shown to act on regions of the
brain involved in reward processing such as the amygdala.

Ghrelin also stimulates the release of growth hormone from the pituitary gland, which, unlike
ghrelin itself, breaks down fat tissue and causes the build-up of muscle.

Ghrelin also has protective effects on the cardiovascular system and plays a role in the control of
insulin release.

How is ghrelin controlled?

Ghrelin levels are primarily regulated by food intake. Levels of ghrelin in the blood rise just before
eating and when fasting, with the timing of these rises being affected by our normal meal routine.
Hence, ghrelin is thought to play a role in mealtime ‘hunger pangs’ and the need to begin meals.
Levels of ghrelin increase when fasting (in line with increased hunger) and are lower in individuals
with a higher body weight compared with lean individuals, which suggests ghrelin could be
involved in the long-term regulation of body weight.

Eating reduces concentrations of ghrelin. Different nutrients slow down ghrelin release to varying
degrees; carbohydrates and proteins restrict the production and release of ghrelin to a greater extent
than fats.

Somatostatin also restricts ghrelin release, as well as many other hormones released from the
digestive tract.

What happens if I have too much ghrelin?

Ghrelin levels increase after dieting, which may explain why diet-induced weight loss can be
difficult to maintain. One would expect higher levels in people with obesity. However, ghrelin
levels are usually lower in people with higher body weight compared with lean people, which
suggests ghrelin is not a cause of obesity; although there is a suggestion that obese people are
actually more sensitive to the hormone. However, more research is needed to confirm this.

Prader-Willi syndrome is a genetic disease in which patients have severe obesity, extreme hunger
and learning difficulties. Unlike more common forms of obesity, circulating ghrelin levels are high

33
 HORMONES

in Prader-Willi syndrome patients and start before the development of obesity. This suggests that
ghrelin may contribute to their increased appetite and body weight.

Ghrelin levels are also high in cachexia and the eating disorder, anorexia nervosa. This may be the
body’s way of making up for weight loss by stimulating food intake and fat storage.

What happens if I have too little ghrelin?

Gastric bypass surgery, which involves reducing the size of the stomach, is considered to be the
most effective treatment for severe, life-threatening obesity. Patients who lose weight after bypass
surgery have been found to have lower ghrelin levels than those who lose weight by other means
such as diet and exercise, which may partly explain the long-lasting success of this treatment.

34
 HORMONES

18. Glucagon
Glucagon is secreted to maintain glucose levels in the bloodstream when fasting and to raise very
low glucose levels.
What is glucagon?
Glucagon is a hormone that is involved in controlling blood sugar (glucose) levels. It is secreted
into the bloodstream by the alpha cells, found in the islets of langerhans, in the pancreas. The
glucagon-secreting alpha cells surround a core of insulin-secreting beta cells, which reflects the
close relationship between the two hormones.

Glucagon’s role in the body is to prevent blood glucose levels dropping too low. To do this, it acts
on the liver in several ways:

It stimulates the conversion of stored glycogen (stored in the liver) to glucose, which can be
released into the bloodstream. This process is called glycogenolysis.
It promotes the production of glucose from amino acid molecules. This process is called
gluconeogenesis.
It reduces glucose consumption by the liver so that as much glucose as possible can be secreted into
the bloodstream to maintain blood glucose levels.
Glucagon also acts on adipose tissue to stimulate the breakdown of fat stores into the bloodstream.

How is glucagon controlled?

Glucagon works along with the hormone insulin to control blood sugar levels and keep them within
set levels. Glucagon is released to stop blood sugar levels dropping too low, while insulin is
released to stop blood sugar levels rising too high.

Release of glucagon is stimulated by low blood glucose (hypoglycaemia), protein-rich meals and
adrenaline (another important hormone for combating low glucose). Release of glucagon is
prevented by raised blood glucose and carbohydrate in meals, detected by cells in the pancreas.

In the longer-term, glucagon is crucial to the body’s response to lack of food. For example, it
encourages the use of stored fat for energy in order to preserve the limited supply of glucose.

What happens if I have too much glucagon?

A rare tumour of the pancreas called a glucagonoma can secrete excessive quantities of glucagon.
This can cause diabetes mellitus, weight loss, venous thrombosis and a characteristic skin rash.

What happens if I have too little glucagon?

Unusual cases of deficiency of glucagon secretion have been reported in babies. This results in
severely low blood glucose which cannot be controlled without administering glucagon.

Glucagon can be given by injection to restore blood glucose lowered by insulin (even in
unconscious patients). It can increase glucose release from glycogen stores more than insulin can

35
 HORMONES

suppress it. The effect of glucagon is limited, so it is very important to eat a carbohydrate meal once
the person has recovered enough to eat safely.

36
 HORMONES

19. Glucagon-like peptide 1

Glucagon-like peptide 1 is a hormone produced in the gut and released in response to food. It causes
reduced appetite and the release of insulin.
Alternative names for glucagon-like peptide 1
GLP-1; incretin; glucagon-like peptide

What is glucagon-like peptide 1?

Glucagon-like peptide 1 belongs to a family of hormones called the incretins, so-called because
they enhance the secretion of insulin. Glucagon-like peptide 1 is a product of a molecule called pre-
proglucagon, a polypeptide which is split to produce many hormones, including glucagon. Because
they come from the same source, these hormones share some similarities, so are called ‘glucagon-
like’. Cells found in the lining of the small intestine (called L-cells) are the major source of
glucagon-like peptide 1, although it is also secreted in smaller quantities by the pancreas and the
central nervous system. Glucagon-like peptide 1 encourages the release of insulin from the
pancreas, increases the volume of cells in the pancreas that produce insulin (beta cells) and holds
back glucagon release. Glucagon-like peptide 1 also increases the feeling of fullness during and
between meals by acting on appetite centres in the brain and by slowing the emptying of the
stomach.

How is glucagon-like peptide 1 controlled?

Food is the main stimulus of glucagon-like peptide 1 release, with increased hormone levels
detectable after 10 minutes of starting to eat and remaining raised in the blood circulation for
several hours after that. The hormone somatostatin holds back the production of glucagon-like
peptide 1.

What happens if I have too much glucagon-like peptide 1?

There are no known cases of too much glucagon-like peptide 1. Recently drugs have been
developed to mimic glucagon-like peptide 1 in the blood circulation to improve the control of
glucose levels in type-2 diabetes. Levels of glucagon-like peptide 1 are also naturally increased
after some types of weight-related surgery, which is thought to contribute to the observed weight
loss and improvement of type-2 diabetes in these patients.

What happens if I have too little glucagon-like peptide 1?

It has been suggested that too little glucagon-like peptide 1 released after a meal may increase the
likelihood of, or worsen, obesity. Since glucagon-like peptide 1 reduces appetite after a meal, if the
body releases less of this hormone, individuals may eat more during a meal and are more likely to
snack between meals. Dieting, or natural weight loss, is linked to a decrease in glucagon-like
peptide 1. The result may be an increased appetite and tendency to regain weight. However, more
research is needed to confirm this.

37
 HORMONES

20. Glucose-dependent insulinotropic peptide

Glucose-dependent insulinotropic peptide is a hormone produced by the small intestine in response
to eating food. Its main action is to encourage the release of insulin into the bloodstream to control
blood sugar levels.
Alternative names for glucose-dependent insulinotropic
peptide
GIP; incretin; gastric inhibitory polypeptide; glucose-dependent insulinotropic polypeptide

What is glucose-dependent insulinotropic peptide?

Glucose-dependent insulinotropic peptide is a hormone released from the small intestine that
enhances the release of insulin following the intake of food. It is a member of the family of
hormones known as the incretins of which the other main member is the hormone glucagon-like
peptide 1.

Glucose-dependent insulinotropic peptide is made and secreted mainly from the upper section of the
small intestine from a specific type of cell known as the K cell. Its main action occurs in the
pancreas where it targets beta cells, which produce insulin. Glucose-dependent insulinotropic
peptide stimulates the release of insulin from the beta cells in the pancreas in order to maintain low
blood sugar levels after eating. It also increases the production of these cells and reduces the rate at
which they break down.

Although this is the main function of glucose-dependent insulinotropic peptide, receptors for
glucose-dependent insulinotropic peptide are also found in other organs of the body where it has
several other effects:

In the brain – glucose-dependent insulinotropic peptide stimulates the growth of cells that have the
ability to divide and eventually develop into nerve cells.
In bone – glucose-dependent insulinotropic peptide increases the formation of bone whilst
decreasing bone breakdown.
Fat tissue – glucose-dependent insulinotropic peptide is known to increase the amount of fat in the
body by increasing the formation of fat cells.
How is glucose-dependent insulinotropic peptide controlled?
The main trigger for glucose-dependent insulinotropic peptide release is food, in particular fatty
foods or those foods that are rich in sugar. Once released into the bloodstream, levels of glucose-
dependent insulinotropic peptide do not remain high for very long. It is broken down quite quickly
(after about seven minutes) and therefore does not remain in the circulating blood for long.
Glucose-dependent insulinotropic peptide release is prevented by the hormone somatostatin,
produced in the pancreas and gastrointestinal tract.

What happens if I have too much glucose-dependent

insulinotropic peptide?

38
 HORMONES

There are currently no known direct causes of too much glucose-dependent insulinotropic peptide.
However, increased levels of glucose-dependent insulinotropic peptide have been linked to both
type 2 diabetes mellitus and obesity. In type 2 diabetes mellitus, some patients have increased levels
of glucose-dependent insulinotropic peptide but it is not known whether this is a cause or
consequence of the condition. In type 2 diabetes mellitus, glucose-dependent insulinotropic peptide
does not function as well as it should so it is less efficient at stimulating insulin release. This means
patients have high blood sugar (hyperglycaemia), which worsens their existing type 2 diabetes
mellitus.

With obesity, scientists believe that by eating too much fatty foods there is an over-production of
glucose-dependent insulinotropic peptide meaning that more fat tissue is produced.

What happens if I have too little glucose-dependent

insulinotropic peptide?
Currently there are no known consequences of having too little glucose-dependent insulinotropic
peptide.

39
 HORMONES

21. Gonadotrophin-releasing hormone

Gonadotrophin-releasing hormone is released from nerve cells in the brain. It controls the
production of luteinising hormone and follicle stimulating hormone from the pituitary gland.
Alternative names for gonadotrophin-releasing hormone
GnRH; gonadotropin-releasing hormone; luliberin; luteinising-hormone-releasing hormone; LHRH;
luteinizing-hormone-releasing hormone

What is gonadotrophin-releasing hormone?

Gonadotrophin-releasing hormone is produced and secreted by specialised nerve cells in the
hypothalamus of the brain. It is released into tiny blood vessels that carry this hormone from the
brain to the pituitary gland, where it stimulates the production of two more hormones – follicle
stimulating hormone and luteinising hormone. These hormones are released into the general
circulation and act on the testes and ovaries to initiate and maintain their reproductive functions.
Follicle stimulating hormone and luteinising hormone control the levels of hormones produced by
the testes and ovaries (such as testosterone, oestradiol and progesterone), and are important in
controlling the production of sperm in men and the maturation and release of an egg during each
menstrual cycle in women.

How is gonadotrophin-releasing hormone controlled?

During childhood, the levels of gonadotrophin-releasing hormone are extremely low, but as puberty
approaches there is an increase in gonadotrophin-releasing hormone, which triggers the onset of
sexual maturation. No one really knows why this occurs, but it probably involves many different
factors.

When the ovaries and testes are fully functional, the production of gonadotrophin-releasing
hormone, luteinising hormone and follicle stimulating hormone are controlled by the levels of
testosterone (in men) and oestrogens (e.g. oestradiol) and progesterone (in women). If the levels of
these hormones rise, the production of gonadotrophin-releasing hormone decreases and vice versa.

There is one exception to this rule; in women, at the midpoint of their menstrual cycle, oestradiol
(produced by the follicle in the ovary that contains the dominant egg) reaches a critical high point.
This stimulates a large increase in gonadotrophin-releasing hormone secretion and, consequently, a
surge of luteinising hormone, which stimulates the release of a mature egg. This process is called
ovulation.

What happens if I have too much gonadotrophin-releasing

hormone?
It is not known what the effects are of having too much gonadotrophin-releasing hormone.
Extremely rarely, pituitary adenomas (tumours) can develop, which increase production of
gonadotrophins leading to overproduction of testosterone or oestrogen.

40
 HORMONES

What happens if I have too little gonadotrophin-releasing

hormone?
A deficiency of gonadotrophin-releasing hormone in childhood means that the individual does not
go through puberty. An example is a rare genetic syndrome known as Kallmann’s syndrome, which
causes loss of the development of gonadotrophin-releasing hormone-producing nerve cells, with a
consequent loss of pubertal development and sexual maturation. It is more common in men than
women and leads to loss of development of the testes or ovaries and infertility.

Any trauma or damage to the hypothalamus can also cause a loss of gonadotrophin-releasing
hormone secretion, which will stop the normal production of follicle stimulating hormone and
luteinising hormone, causing loss of menstrual cycles (amenorrhoea) in women, loss of sperm
production in men, and loss of production of hormones from the testes and ovaries.

41
 HORMONES

22. Growth hormone

Growth hormone is produced by the pituitary gland. It has many functions including maintaining
normal body structure and metabolism.
Alternative names for growth hormone
Somatotropin; GH; human growth hormone; HGH

What is growth hormone?

Growth hormone is released into the bloodstream from the anterior pituitary gland. The pituitary
gland also produces other hormones that have different functions from growth hormone.

Growth hormone acts on many parts of the body to promote growth in children. In adults, it does
not cause growth but it helps to maintain normal body structure and metabolism, including helping
to keep blood glucose levels within set levels.

How is growth hormone controlled?

Growth hormone release is not continuous; it is released in a number of ‘bursts’ or pulses every
three to five hours. Growth hormone release is caused by another hormone (growth hormone-
releasing hormone), which is released from a point higher up in the brain (the hypothalamus) and it
causes the pituitary gland to release the growth hormone.

Growth hormone levels are increased by sleep, stress, exercise and low glucose levels in the blood.
They also increase around the time of puberty. Growth hormone release is lowered in pregnancy
and if the brain senses high levels of growth hormone or insulin-like growth factors already in the
blood. This reduction in growth hormone levels is affected by another hormone called somatostatin.

What happens if I have too much growth hormone?

Not surprisingly, too much growth hormone causes too much growth.

In adults, excessive growth hormone for a long period of time produces a condition known as
acromegaly, in which patients have swelling of the hands and feet and altered facial features. These
patients also have organ enlargement and serious functional disorders such as high blood pressure,
diabetes and heart disease. Over 99% of cases are due to benign tumours of the pituitary gland,
which produce growth hormone. This condition is more common after middle-age when growth is
complete so affected individuals do not get any taller.

Very rarely, increased growth hormone levels can occur in children before they reach their final
height, which can lead to excessive growth of long bones, resulting in the child being abnormally
tall. This is commonly known as gigantism (a very large increase in height).

Overproduction of growth hormone is diagnosed by giving a sugary drink and measuring the
growth hormone level over the next few hours. The sugar should cause growth hormone production
to reduce. However, this does not happen in acromegaly.

42
 HORMONES

What happens if I have too little growth hormone?

Too little growth hormone (deficiency) results in poor growth in children. In adults, it causes a
reduced sense of wellbeing, increased fat, increased risk of heart disease and weak heart, muscles
and bones. The condition may be present from birth where the cause can be unknown, genetic or
due to injury to the pituitary gland (during development or at birth).

Growth hormone deficiency may also develop in adults due to brain injury, a pituitary tumour or
damage to the pituitary gland (for example, after brain surgery or radiotherapy for cancer
treatment). The main treatment is to replace the growth hormone using injections–either once a day
or several times a week.

In the past, growth hormone treatment was stopped at the end of growth. It is now clear that growth
hormone contributes to both bone mass and muscle mass reaching the best possible level, as well as
reducing fat mass during development to an adult. The specialist is therefore likely to discuss the
benefits of continuing growth hormone after growth has completed until age 25 to make sure bone
and muscle mass reach the best possible level. Additionally, growth hormone has been linked to a
sensation of wellbeing, specifically energy levels. There is evidence that 30-50% of adults with
growth hormone deficiency feel tired to a level that impairs their wellbeing. These adults may
benefit from lifelong treatment with growth hormone. Taking growth hormone when adult will not
result in increased height.

43
 HORMONES

23. Growth hormone-releasing hormone

Growth hormone-releasing hormone stimulates the secretion of growth hormone, an important
regulator of growth, metabolism and body structure.
Alternative names for growth hormone-releasing hormone
Growth hormone-releasing factor; GRF; GHRF; GHRH

What is growth hormone-releasing hormone?

Growth hormone-releasing hormone is a hormone produced in the hypothalamus. The principal
function of growth hormone-releasing hormone is to stimulate the pituitary gland to produce and
release growth hormone into the bloodstream. This then acts on virtually every tissue of the body to
control several physical functions and processes. Insulin-like growth factor 1 is a hormone produced
in the liver and other organs in response to growth hormone, which in turn acts in many tissues to
cause metabolic and growth actions. In addition to its effect on growth hormone secretion, growth
hormone-releasing hormone also affects sleep, food intake and memory.

The action of growth hormone-releasing hormone on the pituitary gland is counteracted by

somatostatin, a hormone also produced by the hypothalamus, which prevents growth hormone
release.

How is growth hormone-releasing hormone controlled?

In order to maintain a balanced hormone production, growth hormone-releasing hormone,
somatostatin, growth hormone and insulin-like growth factor 1 levels are regulated by each other.
The consequence of growth hormone-releasing hormone action is an increase in the circulating
levels of growth hormone and insulin-like growth factor 1 which, in turn, act back on the
hypothalamus to prevent growth hormone-releasing hormone production and to stimulate
somatostatin secretion. Somatostatin then prevents the release of growth hormone from the pituitary
gland and growth hormone-releasing hormone production by the hypothalamus, therefore acting as
a powerful suppressor of growth hormone secretion.

Many other factors and physiological conditions such as sleep, stress, exercise and food intake also
affect the hypothalamic release of growth hormone-releasing hormone and somatostatin.

What happens if I have too much growth hormone-releasing

hormone?
Too much growth hormone-releasing hormone production may be caused by hypothalamic tumours
or by tumours located in other parts of the body (ectopic tumours). The consequence of too much
growth hormone-releasing hormone is a rise in growth hormone levels in the bloodstream and, in
many cases, enlargement of the pituitary gland.

In adults, excessive growth hormone for a long period of time produces a condition known as
acromegaly in which patients have swelling of the hands and feet and altered facial features. These
patients also have organ enlargement and serious functional disorders such as high blood pressure,
44
 HORMONES

diabetes and heart disease. An increase in growth hormone before children reach their final height
can lead to excessive growth of long bones, resulting in the child being abnormally tall. This is
commonly known as gigantism.

However, in most cases, growth hormone overproduction is caused by pituitary tumours that
produce growth hormone; only in very rare occasions is excess growth hormone caused by
overproduction of growth hormone-releasing hormone.

What happens if I have too little growth hormone-releasing

hormone?
If the hypothalamus produces too little growth hormone-releasing hormone, the production and
release of growth hormone from the pituitary gland is impaired, leading to a lack of growth
hormone (adult-onset growth hormone deficiency). When a deficiency of growth hormone is
suspected, a ‘growth hormone stimulating test’ is performed using growth hormone-releasing
hormone or other substances, in order to determine the ability of the pituitary gland to release
growth hormone.

Childhood-onset growth hormone deficiency is associated with growth failure and delayed physical
maturity. In adults, the most important consequences of reduced growth hormone levels are changes
in body structure (decreased muscle and bone mass and increased body fat), tiredness, being less
lively and a poor health-related quality of life.

45
 HORMONES

24. Human chorionic gonadotrophin

Human chorionic gonadotrophin is a reproductive hormone that is essential for establishing and
maintaining early pregnancy.
Alternative names for human chorionic gonadotrophin
Human chorionic gonadotrophin; hCG; Novarel; Ovidrel; Pregnyl; A.P.L; Profasi; Chorex;
Chorigon; Chorigon-10

What is human chorionic gonadotrophin?

Photo showing a urine sample that has tested positive for human chorionic gonadotropin (hCG).
This hormone is secreted by the placenta in pregnant women.

Human chorionic gonadotrophin is a hormone produced by the cells that surround the growing
human embryo; these cells will eventually go on to form the placenta. Human chorionic
gonadotrophin can be detected in the urine from 7-9 days post-fertilisation as the embryo attaches
and implants in the womb; it forms the basis of most over-the-counter and hospital pregnancy tests.

During the menstrual cycle, when an egg is released from the ovary at ovulation, the remnants of
the ovarian follicle (which enclosed the egg) form a new, temporary ovarian gland called the corpus
luteum, which produces the hormone progesterone. If, after two weeks, the ovulated egg remains
unfertilised, the corpus luteum stops producing progesterone. Through a feedback mechanism, this
signals the pituitary gland to produce follicle stimulating hormone (and to a lesser extent luteinising
hormone) to initiate the next menstrual cycle. However, in the event that the ovulated egg is
fertilised by sperm and an embryo is conceived, it is vital that the corpus luteum continues to
produce progesterone until the placenta is established (the placenta then takes over progesterone
46
 HORMONES

production). It is important that the corpus luteum keeps producing progesterone because loss of
progesterone leads to shedding of the womb lining (menstruation), which would prevent an embryo
from implanting. Human chorionic gonadotrophin is the embryonic hormone that ensures the
corpus luteum continues to produce progesterone throughout the first trimester of pregnancy.

As well as maintaining progesterone production from the ovary, human chorionic gonadotrophin
may also play a role in making sure the lining of the uterus (endometrium) is ready to receive the
implanting embryo. Recent studies have indicated that human chorionic gonadotrophin may help to
increase the blood supply to the uterus and be involved in re-shaping the lining of the uterus in
preparation for the implanting embryo.

How is human chorionic gonadotrophin controlled?

Human chorionic gonadotrophin is produced by the trophoblast cells which surround the
developing embryo at approximately day five of pregnancy. The amount of human chorionic
gonadotrophin in the bloodstream doubles every 2-3 days as development of the embryo and
placenta continue, and levels peak at around six weeks of pregnancy. Following this peak, levels of
human chorionic gonadotrophin fall (although they remain detectable throughout pregnancy). Once
the placenta is established, it becomes the main source of progesterone production (around week 12
of pregnancy), and human chorionic gonadotrophin is no longer required to maintain ovarian
function. However, human chorionic gonadotrophin may have additional beneficial effects in the
latter stages of pregnancy; such roles are currently being investigated by researchers.

What happens if I have too much human chorionic

gonadotrophin?
There is no strong evidence that high levels of human chorionic gonadotrophin cause direct
negative consequences. Very high levels of human chorionic gonadotrophin are rare but can indicate
hyper-proliferation of the placenta (also referred to as hydatidiform moles or molar pregnancies),
which can lead to cancer (choriocarcinomas) in some cases. Levels of human chorionic
gonadotrophin may also be elevated sometimes in association with some non-pregnancy related
cancers (e.g. kidney, breast, lung and gastrointestinal tract). In such cases, levels of human
chorionic gonadotrophin in the blood/urine can serve as a tumour marker.

In pregnancy, a link between high levels of human chorionic gonadotrophin and occurrence of
Down’s syndrome has also been suggested. Studies have shown that the levels of human chorionic
gonadotrophin in a Down’s syndrome pregnancy are approximately twice that of an unaffected
pregnancy. However, high levels of human chorionic gonadotrophin do not cause Down’s syndrome
(rather it is caused by an extra chromosome at position 21); further research is needed to investigate
this link.

What happens if I have too little human chorionic

gonadotrophin?
Low levels of human chorionic gonadotrophin can indicate a failing pregnancy. Reduced levels of
human chorionic gonadotrophin are often observed in ectopic pregnancies (where the embryo
implants outside of the uterus) or in miscarriages.

47
 HORMONES

25. Insulin
Insulin is an essential hormone produced by the pancreas. Its main role is to control glucose levels
in our bodies.
What is insulin?

Person with diabetes being injected with insulin to regulate their blood sugar levels.

Insulin is a hormone made by an organ located behind the stomach called the pancreas. Here,
insulin is released into the bloodstream by specialised cells called beta cells found in areas of the
pancreas called islets of langerhans (the term insulin comes from the Latin insula meaning island).
Insulin can also be given as a medicine for patients with diabetes because they do not make enough
of their own. It is usually given in the form of an injection.

Insulin is released from the pancreas into the bloodstream. It is a hormone essential for us to live
and has many effects on the whole body, mainly in controlling how the body uses carbohydrate and
fat found in food. Insulin allows cells in the muscles, liver and fat (adipose tissue) to take up sugar
(glucose) that has been absorbed into the bloodstream from food. This provides energy to the cells.
This glucose can also be converted into fat to provide energy when glucose levels are too low. In
addition, insulin has several other metabolic effects (such as stopping the breakdown of protein and
fat).

How is insulin controlled?

When we eat food, glucose is absorbed from our gut into the bloodstream. This rise in blood
glucose causes insulin to be released from the pancreas. Proteins in food and other hormones
produced by the gut in response to food also stimulate insulin release. However, once the blood
glucose levels return to normal, insulin release slows down. In addition, hormones released in times
of acute stress, such as adrenaline, stop the release of insulin, leading to higher blood glucose levels.

48
 HORMONES

The release of insulin is tightly regulated in healthy people in order to balance food intake and the
metabolic needs of the body.

Insulin works in tandem with glucagon, another hormone produced by the pancreas. While insulin’s
role is to lower blood sugar levels if needed, glucagon’s role is to raise blood sugar levels if they fall
too low. Using this system, the body ensures that the blood glucose levels remain within set limits,
which allows the body to function properly.

What happens if I have too much insulin?

People with type 1 diabetes mellitus are given drugs including insulin treatment to lower their high
glucose levels. However, if a person accidentally injects too much insulin, cells will take in too
much glucose from the blood. This leads to abnormally low blood glucose levels (hypoglycaemia).
The body reacts to hypoglycaemia by releasing stored glucose from the liver in an attempt to bring
the levels back to normal. However, persistently low glucose levels in the blood can make a person
feel ill.

Unlike other cells in the body, nerve cells depend almost entirely on glucose as a source of energy.
When the glucose level is too low, the majority of the symptoms result from these nerves not
functioning properly. The brain is particularly affected by low glucose levels. Symptoms include
dizziness, confusion and even coma in severe cases. In addition, the body mounts a ‘fight-back’
response through a specialised set of nerves called the sympathetic nervous system. This causes
palpitations, sweating, hunger, anxiety, tremor and a pale complexion.

What happens if I have too little insulin?

This is commonly seen in people with diabetes and is caused by different pathways in people with
type 1 diabetics compared with people with type 2 diabetes.

In some people, the pancreas is unable to make enough insulin, for example, in a condition called
type 1 diabetes. This condition is caused when the beta cells that produce insulin have been
destroyed. With too little insulin, the body can no longer move glucose from the blood into the cells,
causing high blood glucose levels. If the glucose level is high enough, excess glucose spills into the
urine. This drags extra water into the urine causing more frequent urination and thirst. This leads to
dehydration, which can cause confusion. In addition, with too little insulin, the cells cannot take in
glucose for energy. Other sources of energy (such as fat and muscle) are needed to provide this
energy. This makes the body tired and can cause weight loss. If this continues, patients can become
very ill. This is because the body attempts to make new energy from fat and causes acids to be
produced as waste products. Ultimately, this can lead to coma and death if medical attention is not
sought.

Type 2 diabetes can be caused by two factors. Firstly, the patient’s beta cells may have an impaired
ability to manufacture insulin. This means that while some insulin is produced, it is not enough for
the body’s needs. Secondly, the insulin receptors, which allow insulin to exert its effects on
individual cells, become insensitive and stop responding to the insulin in the bloodstream. A
combination of these factors leads to similar symptoms as seen in type 1 diabetes.

49
 HORMONES

26. Kisspeptin
Kisspeptins are a family of proteins that are essential for fertility. The first gene member of the
family was discovered in 1996 by a group working in Hershey, Pennsylvania. It is named after the
city’s chocolate ‘Kisses’, which are made in Hershey.
Alternative names for kisspeptin
Metastin

What is kisspeptin?
Kisspeptin is produced from the hypothalamus and causes a cascade of cell-cell communication,
ultimately leading to the production of the hormones, luteinising hormone and follicle stimulating
hormone from the pituitary gland, which are released into the blood. These hormones act on testes
and ovaries to produce the sex steroids testosterone and oestradiol, which cause the physical and
emotional changes that are well characterised during puberty.

Kisspeptin has a non-hormonal role too and was originally named metastin after its ability to
prevent the spread of cancer (metastasis).

How is kisspeptin controlled?

Kisspeptin is released together with two other hormones, neurokinin B and dynorphin.
Consequently, the nerve cells making kisspeptin, dynorphin and neurokinin B are popularly referred
to as KNDy (pronounced ‘candy’). We are currently trying to understand exactly what neurokinin B
and dynorphin hormones do, but they appear to control the release of kisspeptin.

What happens if I have too much kisspeptin?

It is not yet clear whether having too much kisspeptin is good or bad, but a few small studies have
linked high levels of kisspeptin during childhood to cases of (early) precocious puberty. More
research is now needed to determine if this is the case.

What happens if I have too little kisspeptin?

When kisspeptin cannot act properly on its target cells in the body, it causes infertility. A clinical
trial has shown that giving kisspeptin to women with infertility and women who do not menstruate
(a condition known as amenorrhoea) can restore the hormone levels in these conditions.
Furthermore, a clinical trial has recently shown that a single injection of kisspeptin can trigger
ovulation (release of eggs), and these eggs can be artificially fertilised, be placed back inside the
womb (in vitro fertilisation), and result in successful pregnancy. Further studies are needed to
determine whether kisspeptin will offer improvements in fertility therapy over existing treatments
for couples with infertility.

Adolescents who have faulty kisspeptin signalling fail to undergo puberty (hypogonadotrophic
hypogonadism), although this is a rare condition.

50
 HORMONES

Recent evidence now suggests kisspeptin might play other roles in the body since it is also present
outside the brain, e.g. in the placenta and the cardiovascular system. For example, levels of
kisspeptin in the blood go up massively (7,000 times!) during pregnancy, although the reason why
is not yet understood. Intriguingly, a few studies have shown that women who have less kisspeptin
in the bloodstream early on in pregnancy may later develop serious complications such as
miscarriage or pre-eclampsia (high blood pressure in the mother, which may cause growth
restriction in the unborn baby). It has been suggested by some that measuring kisspeptin during
early pregnancy may be a useful screening tool to detect pregnancy complications earlier and
hopefully lead to improved care. More research is now needed to determine if this is the case.

51
 HORMONES

27. Leptin
Leptin is a hormone secreted from fat cells that helps to regulate body weight. The name leptin is
derived from the Greek word ‘leptos’ meaning thin. It is sometimes referred to as the ‘Fat
Controller’.
Alternative names for leptin
There are no other names used for the hormone but the gene, which encodes leptin, is known as the
‘ob’ gene.

What is leptin?
Leptin is a hormone released from fat cells in adipose tissue. Leptin signals to the brain, in
particular to an area called the hypothalamus. Leptin does not affect food intake from meal to meal
but, instead, acts to alter food intake and control energy expenditure over the long term. Leptin has
a more profound effect when we lose weight and levels of the hormone fall. This stimulates a huge
appetite and increased food intake. The hormone helps us to maintain our normal weight and
unfortunately for dieters, makes it hard to lose those extra pounds!

How is leptin controlled?

Because leptin is produced by fat cells, the amount of leptin released is directly related to the
amount of body fat; so the more fat an individual has, the more leptin they will have circulating in
their blood. Leptin levels increase if an individual increases their fat mass over a period of time and,
similarly, leptin levels decrease if an individual decreases their fat mass over a period of time.

What happens if I have too much leptin?

Obese people have unusually high levels of leptin. This is because in some obese people, the brain
does not respond to leptin, so they keep eating despite adequate (or excessive) fat stores, a concept
known as ‘leptin resistance’. This causes the fat cells to produce even more leptin. This is similar to
the way people with type 2 diabetes have unusually high levels of insulin, as their body is resistant
to the effects of insulin. The cause of leptin resistance is still unclear.

What happens if I have too little leptin?

There is an extremely rare condition called congenital leptin deficiency, which is a genetic condition
in which the body cannot produce leptin. In the UK, there are only about four families affected by
this genetic condition.

Absence of leptin makes the body think it does not have any fat whatsoever and this results in
uncontrolled food intake and severe childhood obesity. In addition, leptin deficiency may cause
delayed puberty and poor function of the immune system. This condition can be well treated by
leptin injections, which cause dramatic weight loss.

52
 HORMONES

28. Luteinising hormone

Luteinising hormone is produced by the pituitary gland and is one of the main hormones that
control the reproductive system.
Alternative names for luteinising hormone
Interstitial cell stimulating hormone; luteinizing hormone; lutropin; LH

What is luteinising hormone?

Luteinising hormone, like follicle stimulating hormone, is a gonadotrophic hormone produced and
released by cells in the anterior pituitary gland. It is crucial in regulating the function of the testes in
men and ovaries in women.

In men, luteinising hormone stimulates Leydig cells in the testes to produce testosterone, which acts
locally to support sperm production. Testosterone also exerts effects all around the body to generate
male characteristics such as increased muscle mass, enlargement of the larynx to generate a deep
voice, and the growth of facial and body hair.

In women, luteinising hormone carries out different roles in the two halves of the menstrual cycle.
In weeks one to two of the cycle, luteinising hormone is required to stimulate the ovarian follicles in
the ovary to produce the female sex hormone, oestradiol. Around day 14 of the cycle, a surge in
luteinising hormone levels causes the ovarian follicle to tear and release a mature oocyte (egg) from
the ovary, a process called ovulation. For the remainder of the cycle (weeks three to four), the
remnants of the ovarian follicle form a corpus luteum. Luteinising hormone stimulates the corpus
luteum to produce progesterone, which is required to support the early stages of pregnancy, if
fertilisation occurs.

How is luteinising hormone controlled?

The secretion of luteinising hormone from the anterior pituitary gland is regulated through a system
called the hypothalamic-pituitary-gonadal axis. Gonadotrophin-releasing hormone is released from
the hypothalamus and binds to receptors in the anterior pituitary gland to stimulate both the
synthesis and release of luteinising hormone (and follicle stimulating hormone). The released
luteinising hormone is carried in the bloodstream where it binds to receptors in the testes and
ovaries to regulate their hormone secretions and the production of sperm or eggs.

The release of hormones from the gonads can suppress the secretion of gonadotrophin-releasing
hormone and, in turn, luteinising hormone from the anterior pituitary gland. When levels of
hormones from the gonads fall, the reverse happens and gonadtrophin-releasing hormone and hence
luteinising hormone rise. This is known as negative feedback.

In men, testosterone exerts this negative feedback and in women oestrogen and progesterone exert
the same effect except at the midpoint in the menstrual cycle. At this point, high oestrogen
secretions from the ovary stimulate a surge of luteinising hormone from the pituitary gland, which
triggers ovulation.

53
 HORMONES

The fine tuning of luteinising hormone release is vital to maintaining fertility. Because of this,
compounds designed to mimic the actions of gonadotrophin-releasing hormone, luteinising
hormone and follicle stimulating hormone are used to stimulate gonadal function in assisted
conception techniques such as in vitro fertilisation (IVF). Measuring the levels of luteinising
hormone present in urine can be used to predict the timing of the luteinising hormone surge in
women, and hence ovulation. This is one of the methods employed in ovulation prediction kits used
by couples wishing to conceive.

What happens if I have too much luteinising hormone?

Too much luteinising hormone can be an indication of infertility. Since the secretion of luteinising
hormone is tightly controlled by the hypothalamic-pituitary-gonadal axis, high levels of luteinising
hormone in the bloodstream can indicate decreased sex steroid production from the testes or ovaries
(for example, as in premature ovarian failure).

Polycystic ovary syndrome is a common condition in women associated with high levels of
luteinising hormone and reduced fertility. In this condition, an imbalance between luteinising
hormone and follicle stimulating hormone can stimulate inappropriate production of testosterone.

Genetic conditions, such as Klinefelter’s syndrome and Turner syndrome, can also result in high
luteinising hormone levels. Klinefelter’s syndrome is a male-only disorder and results from carrying
an extra X chromosome (so that men have XXY, rather than XY chromosomes). As a result of this,
the testes are small and do not secrete adequate levels of testosterone to support sperm production.
Turner syndrome is a female-only disorder caused by a partial or full deletion of an X chromosome
(so that women have XO, rather than XX). In affected patients, ovarian function is impaired and
therefore luteinising hormone production increases to stimulate ovarian function.

What happens if I have too little luteinising hormone?

Too little luteinising hormone will also result in infertility in both men and women, as a critical
level of luteinising hormone is required to support testicular or ovarian function.

In men, an example of a condition where low levels of luteinising hormone are found is Kallmann’s
syndrome, which is associated with a deficiency in gonadotrophin-releasing hormone secretion from
the hypothalamus.

In women, a lack of luteinising hormone means that ovulation does not occur. An example of a
condition which can be caused by too little luteinising hormone is amenorrhoea.

54
 HORMONES

29. Melanocyte-stimulating hormone

Melanocyte-stimulating hormone describes a group of hormones produced by the pituitary gland,
hypothalamus and skin cells. It is important for protecting the skin from UV rays, development of
pigmentation and control of appetite.
Alternative names for melanocyte-stimulating hormone
MSH; α-melanocyte-stimulating hormone; alpha-MSH; α-MSH; alpha-melanotropin; alpha-
melanocortin; alpha-intermedin; melanophore-stimulating hormone

What is melanocyte-stimulating hormone?

Melanocyte-stimulating hormone is a collective name for a group of peptide hormones produced by
the skin, pituitary gland and hypothalamus in response to ultraviolet (UV) radiation. It plays a key
role in producing coloured pigmentation found in the skin, hair and eyes. It does this by inducing
specialised skin cells called melanocytes to produce a pigment called melanin; melanin protects
cells from DNA damage, which can lead to skin cancer (melanoma).

Melanocyte-stimulating hormone is produced from the same precursor molecule as

adrenocorticotropic hormone called pro-opiomelanocortin (POMC).

Although known for its stimulatory effect on pigment cells, studies have shown that melanocyte-
stimulating hormone can also suppress appetite by acting on receptors in the hypothalamus in the
brain. This effect is enhanced by leptin, a hormone released from fat cells.

Melanocyte-stimulating hormone is also thought to affect a range of other processes in the body; it
has anti-inflammatory effects, can influence the release of the hormone aldosterone, which controls
salt and water balance in the body, and is also thought to have an effect on energy homeostasis and
sexual behaviour. However, further research is needed to clarify the exact role of melanocyte-
stimulating hormone in these processes.

How is melanocyte-stimulating hormone controlled?

Melanocyte-stimulating hormone production is increased by exposure to UV light. Due to the many
other functions of melanocyte-stimulating hormone besides melanin production, there are likely to
be a number of other factors that regulate its production. This means that, unlike most hormones,
melanocyte-stimulating hormone release is not thought to be controlled by a direct feedback
mechanism.

What happens if I have too much melanocyte-stimulating

hormone?
A direct consequence of high levels of melanocyte-stimulating hormone is increased production of
melanin. This can occur as a result of prolonged exposure to the sun or skin tanning. However,
people with a high blood level of melanocyte-stimulating hormone do not necessarily tan very well
or have even skin pigmentation. Very fair-skinned people tend to produce less melanin due to

55
 HORMONES

variations in their melanocyte-stimulating hormone receptors, which means they do not respond to
melanocyte-stimulating hormone levels in the blood.

Hyperpigmentation or abnormal darkening of the skin is found in patients with primary adrenal
insufficiency (Addison’s disease). In Addison’s disease, the adrenal glands do not produce enough
hormones (including cortisol). This leads to a positive feedback loop where the hypothalamus
stimulates the pituitary gland to release more adrenocorticotropic hormone to try and stimulate the
adrenal glands to produce more cortisol. Adrenocorticotropic hormone can be broken down to
produce melanocyte-stimulating hormone, leading to hyperpigmentation of the skin.

Melanocyte-stimulating hormone levels are also raised during pregnancy and in women using birth
control pills, which can cause hyperpigmentation of the skin. Cushing’s syndrome, due to an excess
production of adrenocorticotropic hormone, can also lead to hyperpigmentation.

What happens if I have too little melanocyte-stimulating

hormone?
A deficiency in melanocyte-stimulating hormone results in a lack of skin pigmentation and
subsequent loss of natural protection from UV rays of the sun. In secondary adrenal insufficiency,
damage to the pituitary gland prevents release of adrenocorticotropic hormone and melanocyte-
stimulating hormone and there is reduced pigmentation of the skin. Melanocyte-stimulating
hormone deficiency can cause increased inflammation, pain, and sleeping problems, as well as a
reduction in the levels of anti-diuretic hormone, which causes thirst and frequent urination.
Melanocyte-stimulating hormone deficiency may also result in increased food intake and obesity.

56
 HORMONES

30. Melatonin
Melatonin is mainly produced by the pineal gland and, although it appears not to be essential for
human physiology, it is known to have a range of different effects when taken as a medication.
Alternative names for melatonin
N-acetyl-5-methoxytryptamine

What is melatonin?

Melatonin (blue) is produced naturally by the pineal gland (purple) at night-time indicated by light
entering the eyes (left), and by the arrow showing the melatonin secretion signal sent by the optic
nerve to the pineal gland once darkness has fallen.

Melatonin is produced by various tissues in the body, although the major source is the pineal gland
in the brain. The production and release of melatonin from the pineal gland occurs with a clear daily
(circadian) rhythm, with peak levels occurring at night. Melatonin is carried by the circulation from
the brain to all areas of the body. Tissues expressing proteins called receptors specific for melatonin
are able to detect the peak in circulating melatonin at night and this signals to the body that it is
night-time. The level of circulating melatonin can be detected in samples of blood and saliva, and
this is used in clinical research to identify internal circadian rhythms.

In many animals (including a wide range of mammals and birds), melatonin from the pineal gland is
essential for the regulation of the body’s seasonal biology (e.g. reproduction, behaviour and coat
growth) in response to changing day length. The importance of pineal melatonin in human biology
is not clear, although it may help to synchronise circadian rhythms in different parts of the body.

57
 HORMONES

Melatonin has often been called a ‘sleep hormone’–although it is not essential for human sleep, we
sleep better during the time that melatonin is secreted.

Association between tumours of the pineal gland and the timing of puberty suggests that melatonin
may have a minor role in reproductive development, although the mechanism of this action is
uncertain.

In addition to its production in the body, melatonin can also be taken in capsule form. When
administered at an appropriate time of day, it can reset the body’s circadian rhythms (see the articles
on jet lag and circadian rhythm sleep disorders). This resetting effect of melatonin has been reported
for many dose strengths, including those that are equivalent to the concentration of melatonin
naturally produced by the pineal gland. Higher doses of melatonin can reset circadian rhythms,
bring on sleepiness and lower core body temperature.

How is melatonin controlled?

In humans and other mammals, the daily rhythm of pineal melatonin production is driven by the
‘master’ circadian clock. This ‘clock’ is in a region of the brain called the suprachiasmatic nuclei,
which expresses a series of genes termed clock genes that continuously oscillate throughout the day.
This is synchronised to the solar day via light input from the eyes. The suprachiasmatic nuclei link
to the pineal gland through a complex pathway in the nervous system, passing through different
brain areas, into the spinal cord and then finally reaching the pineal gland. During the day, the
suprachiasmatic nuclei stops melatonin production by sending inhibitory messages to the pineal
gland. At night however, the suprachiasmatic nuclei are less active, and the inhibition exerted
during the day is reduced resulting in melatonin production by the pineal gland.

Light is an important regulator of melatonin production from the pineal gland. Firstly, it can reset a
specific area of the brain (the suprachiasmatic nuclei clock) and, as a result, the timing of the
melatonin production. Secondly, exposure to light during the body’s biological night reduces
melatonin production and release.

What happens if I have too much melatonin?

There are large variations in the amount of melatonin produced by individuals and these are not
associated with any health problems. The main consequences of swallowing large amounts of
melatonin are drowsiness and reduced core body temperature. Very large doses have effects on the
performance of the human reproductive system. There is also evidence that very high
concentrations of melatonin have an antioxidant effect, although the purpose of this has not yet been
established.

What happens if I have too little melatonin?

Reduced melatonin production is not known to have any effect on health.

58
 HORMONES

31. Oestradiol
Oestradiol is a powerful reproductive hormone that has a wide range of actions in both men and
women.
Alternative names for oestradiol
E2; estradiol; 17-beta (o)estradiol

What is oestradiol?
Oestradiol is a steroid hormone made from cholesterol and is the strongest of the three naturally
produced oestrogens. It is the main oestrogen found in women and has many functions, although it
mainly acts to mature and maintain the female reproductive system. A natural boost in oestradiol
levels during the menstrual cycle causes an egg to mature and be released, as well as thickening the
uterus lining so that the egg can implant if it becomes fertilised. Oestradiol also promotes
development of breast tissue and increases bone and cartilage thickness.

In premenopausal women, oestradiol is mostly made by the ovaries. Oestradiol levels vary
throughout the monthly menstrual cycle, being highest at ovulation and lowest at menstruation.
Oestradiol levels in women reduce slowly with age, with a large decrease occurring at the
menopause when the ovaries switch off.

Men also produce oestradiol. It is made in the same pathway as testosterone. However, levels are
much lower than in women. In both sexes, oestradiol is also made in much smaller amounts by fat
tissue, the brain and the walls of blood vessels.

How is oestradiol controlled?

Production of oestradiol in women’s ovaries involves a chain reaction of hormones known as the
hypothalamic-pituitary-gonadal axis. This begins with the hypothalamus in the base of the brain,
which releases a hormone called gonadotropin-releasing hormone. In turn, this makes the pituitary
gland release two further hormones, luteinising hormone and follicle stimulating hormone. They
enter the blood and stimulate the ovary and immature follicles containing an egg. These begin to
produce oestradiol. Communication between oestradiol levels in the circulation and the brain
controls development of an egg, ovulation and the menstrual cycle.

What happens if I have too much oestradiol?

Too much oestradiol can have a number of effects. In mild cases, excess levels cause acne,
constipation, loss of libido and depression. More severe effects can include uterine and breast
cancer, female infertility, weight gain, stroke and heart attack.

In men, too much oestradiol can also cause sexual dysfunction, loss of muscle tone, increased body
fat and development of female characteristics, such as breast tissue. Oestradiol becomes more
dominant as a man ages and his testosterone production reduces, which scientists think may be a
contributing factor in the development of prostate cancer.

59
 HORMONES

Oestradiol is used in hormone replacement therapy to relieve symptoms of the menopause in

women. There are many recognised pros and cons to hormone replacement therapy. See the article
on menopause for more information.

What happens if I have too little oestradiol?

Oestradiol is necessary for bone development, so people with low oestradiol tend to have skeletal
problems like inadequate bone growth and osteoporosis. Girls will also encounter problems at
puberty such as a delay in, or failure of, breast development, a disrupted or absent menstrual cycle
and infertility. Oestradiol also has important roles in the brain, where low levels can cause
depression, fatigue and mood swings.

A woman’s oestradiol production falls naturally at the menopause and causes many of its
symptoms. Initially these include night sweats, hot flushes, vaginal dryness and mood swings,
whilst in the long term she is more likely to develop osteoporosis.

60
 HORMONES

32. Oestriol
Oestriol is a hormone made during pregnancy that can be used to measure foetal health and predict
when birth may happen.
Alternative names for oestriol
E3; estriol

What is oestriol?
Oestriol is one of three oestrogens naturally produced by women. Normally, levels in the body are
very low, but during pregnancy, it is made in much higher amounts by the placenta. Oestriol levels
increase throughout pregnancy and are highest just before birth. It is an indicator of the health of the
unborn foetus because the chemical from which it is made comes exclusively from the adrenal
glands of the baby. It causes growth of the uterus and increases its sensitivity to other pregnancy-
related hormones, thus causing a gradual preparation for birth. Oestriol levels start to increase from
week eight of pregnancy and scientists now think that labour begins when oestriol becomes the
dominant hormone.

How is oestriol controlled?

Oestriol is made by the placenta from a chemical that comes from the foetal adrenal gland called
dehydroepiandrosterone sulphate. Oestriol levels increase throughout pregnancy because it stops
other hormones from preventing dehydroepiandrostene sulphate being produced and thus allows
more oestriol to be made.

What happens if I have too much oestriol?

A sudden surge in oestriol happens around three weeks before labour. If the surge comes early, this
can suggest a premature birth.

Some hormone replacement therapy (HRT) preparations contain oestriol. Although the body
removes oestriol much faster than other oestrogens, there are positives and negatives to its use in
HRT.

What happens if I have too little oestriol?

In non-pregnant women, oestriol only exists at very low levels. Too little oestriol during pregnancy
can indicate that there are problems with the baby, such as Down’s syndrome or problems with the
placenta. Later in pregnancy, comparatively low oestriol indicates that labour may not come on its
own, but will have to be induced.

61
 HORMONES

33. Oestrone
Oestrone is a hormone produced by the ovaries. It is one of the major oestrogens in postmenopausal
women.
Alternative names for oestrone
E1; estrone

What is oestrone?
Oestrone is one of three types of oestrogen made by the body. The other types of oestrogen are
called oestradiol and oestriol. Oestrone is primarily produced by the ovaries as well as by adipose
tissue and the adrenal glands. It has a much weaker biological activity than oestradiol. Oestrone is
the major type of oestrogen hormone produced in any quantities in postmenopausal women.

How is oestrone controlled?

Very little is known about how the production of oestrone is controlled. In premenopausal women,
about 50% of oestrone is produced by the ovaries. The remaining 50% is produced by fat tissue and
the adrenal glands, which are also the sources of oestrone in children, men and postmenopausal
women. Because oestrone is less active than oestradiol, it is thought that oestrone may act as a
reservoir that can be converted into oestradiol as needed.

What happens if I have too much oestrone?

Increased oestrone production can occur in women with breast cancer and in men undergoing
treatment for testicular or prostate cancer (which reduces testosterone production). Obese women
also produce more oestrone from their fat tissues. Overproduction of oestrone may be associated
with the development of breast and endometrial cancer in women. Aside from this oestrone
production may affect health in both positive and negative ways, but the full extent of this is
currently not known.

What happens if I have too little oestrone?

Low levels of oestrogens cause osteoporosis, fatigue, hot flushes, loss of libido and depression. As
oestrone is the main oestrogen in postmenopausal women, it is thought that low levels may worsen
these symptoms (which are also common during the menopause), particularly in the case of
osteoporosis. However, further research is needed to confirm this.

62
 HORMONES

34. Oxytocin
Oxytocin is a hormone that acts on organs in the body (including the breast and uterus) and as a
chemical messenger in the brain, controlling key aspects of the reproductive system, including
childbirth and lactation, and aspects of human behaviour.
Alternative names for oxytocin
Alpha-hypophamine; manufactured versions – carbetocin, syntocinon and pitocin

What is oxytocin?
Oxytocin is produced in the hypothalamus and is secreted into the bloodstream by the posterior
pituitary gland. Secretion depends on electrical activity of neurons in the hypothalamus – it is
released into the blood when these cells are excited.

The two main actions of oxytocin in the body are contraction of the womb (uterus) during childbirth
and lactation. Oxytocin stimulates the uterine muscles to contract and also increases production of
prostaglandins, which increase the contractions further. Manufactured oxytocin is sometimes given
to induce labour if it has not started naturally or it can be used to strengthen contractions to aid
childbirth. In addition, manufactured oxytocin is often given to speed up delivery of the placenta
and reduce the risk of heavy bleeding by contracting the uterus. During breastfeeding, oxytocin
promotes the movement of milk into the breast, allowing it to be excreted by the nipple. Oxytocin is
also present in men, playing a role in sperm movement and production of testosterone by the testes.

More recently, oxytocin has been suggested to be an important player in social behaviour.

In the brain, oxytocin acts as a chemical messenger and has been shown to be important in human
behaviours including sexual arousal, recognition, trust, anxiety and mother–infant bonding. As a
result, oxytocin has been called the ‘love hormone’ or ‘cuddle chemical’.

Many research projects are undertaken, looking at the role of oxytocin in addiction, brain injury,
anorexia and stress, among other topics.

How is oxytocin controlled?

Oxytocin is controlled by a positive feedback mechanism where release of the hormone causes an
action that stimulates more of its own release. When contraction of the uterus starts, for example,
oxytocin is released, which stimulates more contractions and more oxytocin to be released. In this
way, contractions increase in intensity and frequency.

There is also a positive feedback involved in the milk-ejection reflex. When a baby sucks at the
breast of its mother, the stimulation leads to oxytocin secretion into the blood, which then causes
milk to be let down into the breast. Oxytocin is also released into the brain to help stimulate further
oxytocin secretion. These processes are self-limiting; production of the hormone is stopped after the
baby is delivered or when the baby stops feeding.

What happens if I have too much oxytocin?

63
 HORMONES

At present, the implications of having too much oxytocin are not clear. High levels have been linked
to benign prostatic hyperplasia, a condition which affects the prostate in more than half of men over
the age of 50. This may cause difficulty in passing urine.

It may be possible to treat this condition by manipulating oxytocin levels; however, more research
is needed before any possible treatments are available.

What happens if I have too little oxytocin?

Similarly, it is not fully understood at present if there are any implications of having too little
oxytocin in the body. A lack of oxytocin in a nursing mother would prevent the milk-ejection reflex
and prevent breastfeeding.

Low oxytocin levels have been linked to autism and autistic spectrum disorders (e.g. Asperger
syndrome) – a key element of these disorders being poor social functioning. Some scientists believe
oxytocin could be used to treat these disorders. In addition, low oxytocin has been linked to
depressive symptoms and it has been proposed as a treatment for depressive disorders. However,
there is not enough evidence at present to support its use for any of these conditions.

64
 HORMONES

35. Parathyroid hormone

Parathyroid hormone is secreted by the parathyroid glands and is the most important regulator of
blood calcium levels.
Alternative names for parathyroid hormone
PTH; parathormone; parathyrin

What is parathyroid hormone?

The parathyroid glands are located in the neck, just behind the butterfly-shaped thyroid gland.

Parathyroid hormone is secreted from four parathyroid glands, which are small glands in the neck,
located behind the thyroid gland. Parathyroid hormone regulates calcium levels in the blood, largely
by increasing the levels when they are too low. It does this through its actions on the kidneys, bones
and intestine:

1. Bones – parathyroid hormone stimulates the release of calcium from large calcium stores in
the bones into the bloodstream. This increases bone destruction and decreases the formation
of new bone.
2. Kidneys – parathyroid hormone reduces loss of calcium in urine. Parathyroid hormone also
stimulates the production of active vitamin d in the kidneys.
3. Intestine – parathyroid hormone indirectly increases calcium absorption from food in the
intestine, via its effects on vitamin D metabolism.
How is parathyroid hormone controlled?

65
 HORMONES

Parathyroid hormone is mainly controlled by the negative feedback of calcium levels in the blood to
the parathyroid glands. Low calcium levels in the blood stimulate parathyroid hormone secretion,
whereas high calcium levels in the blood prevent the release of parathyroid hormone.

What happens if I have too much parathyroid hormone?

A primary problem in the parathyroid glands, producing too much parathyroid hormone causes
raised calcium levels in the blood (hypercalcaemia) and this is referred to as primary
hyperparathyroidism. There is a similar but much rarer condition called tertiary
hyperparathyroidism that causes hypercalcaemia due to excess parathyroid hormone production on
the back drop of all four glands being overactive. Secondary hyperparathyroidism occurs in
response to low blood calcium levels and is caused by other mechanisms, for example, kidney
disease and vitamin D deficiency.

Mild primary hyperparathyroidism often causes few if any symptoms and is frequently diagnosed
by finding a high calcium concentration on a routine blood test. Treatment may be by surgical
removal of the affected gland(s) (parathyroidectomy). Further information on the symptoms for
each condition can be found in the individual articles.

What happens if I have too little parathyroid hormone?

Too little parathyroid hormone or hypoparathyroidism, is a rare medical condition. It can result in
low levels of calcium in the blood (hypocalcaemia). It is usually treated medically with oral calcium
and vitamin D analogues but the availability of parathyroid hormone replacement therapy may
change the approach to treatment for some patients.

66
 HORMONES

36. Peptide YY
Peptide YY is a hormone made in the small intestine. It helps to reduce appetite and limit food
intake.
Alternative names for peptide YY
PYY; peptide tyrosine tyrosine; pancreatic peptide YY3-36; pancreatic peptide YY

What is peptide YY?

The full name for peptide YY is pancreatic peptide YY. It is a hormone that is secreted from
endocrine cells called L-cells in the small intestine. There are two major forms of the peptide; one is
36 amino acids long (PYY1-36) and the other lacks the first two amino acids (PYY3-36). It is
secreted alongside the hormone glucagon-like peptide 1. Peptide YY is released after eating,
circulates in the blood and works by binding to receptors in the brain. These receptors then cause a
decreased appetite and make people feel full after eating. Peptide YY also acts in the stomach and
intestine to slow down the movement of food through the digestive tract.

How is peptide YY controlled?

Peptide YY secretion is mainly stimulated by the presence of food in the digestive tract, particularly
fat and protein. The amount of peptide YY that is released into the blood depends on the amount of
calories eaten, with higher calorie foods causing more peptide YY release than lower calorie foods.
Peptide YY secretion can also be stimulated by digestive juices (such as bile) and another
gastrointestinal hormone called cholecystokinin. The highest levels of peptide YY are found in the
second hour after eating. Peptide YY levels then gradually decrease. Low levels of peptide YY are
seen during long periods without eating, for example overnight.

What happens if I have too much peptide YY?

High peptide YY concentrations are unusual. They will cause a decrease in appetite and food intake.
High peptide YY concentrations are associated with diseases where there is dramatic weight loss,
such as anorexia nervosa, coeliac disease, inflammatory bowel disease (Crohn’s disease and
ulcerative colitis) and some cancers.

What happens if I have too little peptide YY?

Low peptide YY concentrations are associated with an increase in appetite and food intake. Low
peptide YY levels are seen in obesity and before the onset of type 2 diabetes and may contribute to
weight gain in these conditions. However, low peptide YY concentrations are very unlikely to be
the main cause of obesity as the levels decrease after weight gain has started. There has been some
research into using peptide YY as a medication for obesity, aiming to decrease the appetite of
people who are overweight. This research is still ongoing.

It is extremely rare to have a genetic deficiency of peptide YY.

67
 HORMONES

37. Progesterone
Progesterone is a hormone released by the corpus luteum in the ovary. It plays important roles in the
menstrual cycle and in maintaining the early stages of pregnancy. It may also be involved in the
growth of certain cancers.
What is progesterone?
Progesterone belongs to a group of steroid hormones called progestogens. It is mainly secreted by
the corpus luteum in the ovary during the second half of the menstrual cycle. It plays important
roles in the menstrual cycle and in maintaining the early stages of pregnancy.

During the menstrual cycle, when an egg is released from the ovary at ovulation (approximately day
14), the remnants of the ovarian follicle that enclosed the developing egg form a structure called the
corpus luteum. This releases progesterone and, to a lesser extent, oestradiol. The progesterone
prepares the body for pregnancy in the event that the released egg is fertilised. If the egg is not
fertilised, the corpus luteum breaks down, the production of progesterone falls and a new menstrual
cycle begins.

If the egg is fertilised, progesterone stimulates the growth of blood vessels that supply the lining of
the womb (endometrium) and stimulates glands in the endometrium to secrete nutrients that nourish
the early embryo. Progesterone then prepares the tissue lining of the uterus to allow the fertilised
egg to implant and helps to maintain the endometrium throughout pregnancy. During the early
stages of pregnancy, progesterone is still produced by the corpus luteum and is essential for
supporting the pregnancy and establishing the placenta. Once the placenta is established, it then
takes over progesterone production at around week 12 of pregnancy. During pregnancy,
progesterone plays an important role in the development of the foetus; stimulates the growth of
maternal breast tissue; prevents lactation; and strengthens the pelvic wall muscles in preparation for
labour. The level of progesterone in the body steadily rises throughout pregnancy until labour
occurs and the baby is born.

Although the corpus luteum in the ovaries is the major site of progesterone production in humans,
progesterone is also produced in smaller quantities by the ovaries themselves, the adrenal glands
and, during pregnancy, the placenta.

How is progesterone controlled?

The formation of the corpus luteum (which produces the majority of progesterone) is triggered by a
surge in luteinising hormone production by the anterior pituitary gland. This normally occurs at
approximately day 14 of the menstrual cycle and it stimulates the release of an egg from the ovary
and the formation of the corpus luteum. The corpus luteum then releases progesterone, which
prepares the body for pregnancy. If the egg is not fertilised and no embryo is conceived, the corpus
luteum breaks down and the production of progesterone decreases. As the lining of the womb is no
longer maintained by progesterone from the corpus luteum, it breaks away and menstrual bleeding
occurs, marking the start of a new menstrual cycle.

However, if the ovulated egg is fertilised and gives rise to an embryo, the cells that surround this
early embryo (which are destined to form the placenta) will secrete human chorionic gonadotrophin.
This hormone has a very similar chemical structure to luteinising hormone. This means it can bind

68
 HORMONES

to and activate the same receptors as luteinising hormone, meaning that the corpus luteum does not
break down and instead keeps producing progesterone until the placenta is established.

What happens if I have too much progesterone?

There are no known serious medical consequences of having too much progesterone. Levels of
progesterone do increase naturally in pregnancy as mentioned above.

High levels of progesterone are associated with the condition congenital adrenal hyperplasia.
However, the high progesterone levels are a consequence of and not a cause of this condition. Also,
high levels of progesterone are associated with an increased risk for developing breast cancer.

Progesterone, either alone or in combination with oestrogen, is taken by women as an oral

contraceptive (‘the pill’). ‘The pill’ works by preventing ovulation, making it nearly 100% effective
in preventing pregnancy.

Progesterone is used in hormone replacement therapy to relieve symptoms of the menopause in

women. There are many recognised pros and cons to hormone replacement therapy – see the article
on menopause for more information.

What happens if I have too little progesterone?

If progesterone is absent or levels are too low, irregular and heavy menstrual bleeding can occur. A
drop in progesterone during pregnancy can result in a miscarriage and early labour. Mothers at risk
of giving birth too soon can be given a synthetic form of progesterone to delay the onset of labour.

Lack of progesterone in the bloodstream can mean the ovary has failed to release an egg at
ovulation, as can occur in women with polycystic ovary syndrome.

69
 HORMONES

38. Prolactin
Prolactin is a hormone produced in the pituitary gland, named because of its role in lactation. It also
has other wide ranging functions in the body, from acting on the reproductive system to influencing
behaviour and regulating the immune system.
Alternative names for prolactin
In everyday language, prolactin is referred to as the ‘milk hormone’; PRL; luteotropic hormone;
LTH

What is prolactin?
Prolactin is a hormone named originally after its function to promote milk production (lactation) in
mammals in response to the suckling of young after birth. It has since been shown to have more
than 300 functions in the body. These can be divided into a number of areas: reproductive,
metabolic, regulation of fluids (osmoregulation), regulation of the immune system
(immunoregulation) and behavioural functions.

In humans, prolactin is produced both in the front portion of the pituitary gland (anterior pituitary
gland) and in a range of sites elsewhere in the body. Lactotroph cells in the pituitary gland produce
prolactin, where it is stored and then released into the bloodstream. Human prolactin is also
produced in the uterus, immune cells, brain, breasts, prostate, skin and adipose tissue.

How is prolactin controlled?

One of the main regulators of the production of prolactin from the pituitary gland is the hormone
called dopamine, which is produced by the hypothalamus, the part of the brain directly above the
pituitary gland. Dopamine restrains prolactin production, so the more dopamine there is, the less
prolactin is released. Prolactin itself enhances the secretion of dopamine, so this creates a negative
feedback loop.

Oestrogen is another key regulator of prolactin and has been shown to increase the production and
secretion of prolactin from the pituitary gland. Studies have shown small increases in prolactin in
the blood circulation of women during stages of their reproductive cycle where oestrogen levels are
at their highest. This is also the case during and after pregnancy, which makes sense, since a higher
level of circulating prolactin is needed to cause lactation to start.

In addition to dopamine and oestrogen, a whole range of other hormones can both increase and
decrease the amount of prolactin released in the body, with some examples being thyrotropin-
releasing hormone, oxytocin and anti-diuretic hormone.

What happens if I have too much prolactin?

The condition of having too much prolactin circulating in the blood is called hyperprolactinaemia.
The most common causes of hyperprolactinaemia include pregnancy, medications that reduce
dopamine action in the body, thyroid underactivity and benign pituitary tumours (known as
prolactinomas). Symptoms can include the unwanted production of milk, disturbances to the

70
 HORMONES

menstrual cycle and symptoms due to oestrogen deficiency (in women) or testosterone deficiency
(in men). The vast majority of patients with a prolactinoma can be treated successfully using drugs
which mimic the action of dopamine. The most commonly used is cabergoline.

What happens if I have too little prolactin?

The condition of having too little prolactin circulating in the blood is called hypoprolactinaemia.
This condition is very rare and may occur in people with pituitary underactivity.

A decrease in the amount of prolactin secreted can lead to insufficient milk being produced after
giving birth. Most people with low prolactin levels do not have any specific medical problems,
although preliminary evidence suggests they might have reduced immune responses to some
infections.

71
 HORMONES

39. Prostaglandins
The prostaglandins are a group of lipids made at sites of tissue damage or infection that are
involved in dealing with injury and illness. They control processes such as inflammation, blood
flow, the formation of blood clots and the induction of labour.
Alternative names for prostaglandins
Prostaglandin D ; prostaglandin E ; prostaglandin F ; prostaglandin I (which is also known as
2 2 2 2

prostacyclin); a closely related lipid called thromboxane

What are prostaglandins?

Mechanism of action of the drug aspirin. Aspirin works by stopping prostaglandin being made:
aspirin molecules (blue hexagons) enter the cell and chemically modify the cyclooxygenase enzyme
(purple) to prevent prostaglandin being made.

Unlike most hormones, the prostaglandins are not secreted from a gland to be carried in the
bloodstream and work on specific areas around the body. Instead, they are made by a chemical
reaction at the site where they are needed and can be made in nearly all the organs in the body.
Prostaglandins are part of the body’s way of dealing with injury and illness.

The prostaglandins act as signals to control several different processes depending on the part of the
body in which they are made. Prostaglandins are made at sites of tissue damage or infection, where
they cause inflammation, pain and fever as part of the healing process. When a blood vessel is
injured, a prostaglandin called thromboxane stimulates the formation of a blood clot to try to heal
the damage; it also causes the muscle in the blood vessel wall to contract (causing the blood vessel
to narrow) to try to prevent blood loss. Another prostaglandin called prostacyclin has the opposite
effect to thromboxane, reducing blood clotting and removing any clots that are no longer needed; it
also causes the muscle in the blood vessel wall to relax, so that the vessel dilates. The opposing
effects that thromboxane and prostacyclin have on the width of blood vessels can control the
amount of blood flow and regulate response to injury and inflammation.

Prostaglandins are also involved in regulating the contraction and relaxation of the muscles in the
gut and the airways.

72
 HORMONES

Prostaglandins are known to regulate the female reproductive system, and are involved in the
control of ovulation, the menstrual cycle and the induction of labour. Indeed, manufactured forms of
prostaglandins–prostaglandin E and F can be used to induce (kick-start) labour.
2 2

How are prostaglandins controlled?

The chemical reaction that makes the prostaglandins involves several steps; the first step is carried
out by an enzyme called cyclooxygenase. There are two main types of this enzyme:
cyclooxygenase-1 and cyclooxygenase-2. When the body is functioning normally, baseline levels of
prostaglandins are produced by the action of cyclooxygenase-1. When the body is injured (or
inflammation occurs in any area of the body), cyclooxygenase-2 is activated and produces extra
prostaglandins, which helps the body to respond to the injury.

Prostaglandins carry out their actions by acting on specific receptors; at least eight different
prostaglandin receptors have been discovered. The presence of these receptors in different organs
throughout the body allows the different actions of each prostaglandin to be carried out, depending
on which receptor they interact with.

Prostaglandins are very short-lived and are broken down quickly by the body. They only carry out
their actions in the immediate vicinity of where they are produced; this helps to regulate and limit
their actions.

What happens if I have too much prostaglandins?

High levels of prostaglandins are produced in response to injury or infection and cause
inflammation, which is associated with the symptoms of redness, swelling, pain and fever. This is
an important part of the body’s normal healing process.

However, this natural response can sometimes lead to excess and chronic production of
prostaglandins, which may contribute to several diseases by causing unwanted inflammation. This
means that drugs, which specifically block cyclooxygenase-2, can be used to treat conditions such
as arthritis, heavy menstrual bleeding and painful menstrual cramps and certain types of cancer,
including colon and breast cancer. New discoveries are being made about cyclooxygenases which
suggest that cyclooxygenase-2 is not just responsible for disease but has other functions.

Anti-inflammatory drugs, such as aspirin and ibuprofen, work by blocking the action of the
cyclooxygenase enzymes and so reduce prostaglandin levels. This is how these drugs work to
relieve the symptoms of inflammation. Aspirin also blocks the production of thromboxane and so
can be used to prevent unwanted blood clotting in patients with heart disease.

What happens if I have too few prostaglandins?

Manufactured prostaglandins can be used to increase prostaglandin levels in the body under certain
circumstances. For example, administration of prostaglandins can induce labour at the end of
pregnancy or abortion in the case of an unwanted pregnancy. They can also be used to treat stomach
ulcers, glaucoma and congenital heart disease in newborn babies. Further advances in understanding
how prostaglandins work may lead to newer treatments for a number of conditions.

73
 HORMONES

40. Relaxin
Relaxin is a hormone produced by the ovary and the placenta with important effects in the female
reproductive system and during pregnancy. In preparation for childbirth, it relaxes the ligaments in
the pelvis and softens and widens the cervix.
What is relaxin?
In women, relaxin is secreted into the circulation by the corpus luteum in the ovary. During
pregnancy it is also released from the placenta, the membranes which surround the foetus, and the
lining of the uterus. In men, relaxin is secreted from the prostate gland and can be detected in the
semen, but is not generally found in the blood circulation.

The effects of relaxin are most well-described during the female reproductive cycle and pregnancy.
Relaxin levels in the circulation rise after ovulation, during the second half of the menstrual cycle.
At this stage it is thought to relax the wall of the uterus by inhibiting contractions, and it also
prepares the lining of the uterus for pregnancy. If pregnancy does not occur, relaxin levels drop
again. During pregnancy, relaxin levels are at their highest in the first trimester. At this time it is
believed to promote implantation of the developing foetus into the wall of the uterus and the growth
of the placenta. Early in pregnancy, relaxin also inhibits contractions in the wall of the uterus, to
prevent premature childbirth. Relaxin can regulate the mother’s cardiovascular and renal systems to
help them adapt to the increase in demand for oxygen and nutrients for the foetus, and to process
the resulting waste products. It is thought to do this by relaxing the mother’s blood vessels to
increase blood flow to the placenta and kidneys.

Towards the end of pregnancy relaxin promotes rupture of the membranes surrounding the foetus
and the growth, opening and softening of the cervix and vagina to aid the process of childbirth.
There is also some evidence that relaxin can relax the ligaments at the front of the pelvis to ease
delivery of the baby. There are several other factors involved in labour, but the exact trigger remains
unclear.

The role of relaxin in men is less clear. However, there is evidence that it may increase the
movement of sperm cells in the semen.

Relaxin belongs to the same family of hormones as insulin. Over the last decade, several relaxin-
like peptides have been discovered, although the function of these peptides remains unclear.

Recent studies have revealed effects of relaxin on other systems in the body. Relaxin decreases
tissue fibrosis in the kidney, heart, lungs and liver, and promotes wound healing. Tissue fibrosis is
the formation of hard tissue as a result of inflammation which can lead to scarring and loss of organ
function. This has made relaxin of interest to scientists studying how the heart heals after it has been
damaged, which may help to treat heart failure in the future. In addition, relaxin can influence blood
pressure by relaxing blood vessels; promote the growth of new blood vessels; and is also anti-
inflammatory. All of these properties could make it a potential therapeutic target for the treatment of
certain diseases.

How is relaxin controlled?

The control of relaxin release in humans is not fully understood. It is believed that relaxin
production by the ovary during the menstrual cycle is stimulated by luteinising hormone from the
74
 HORMONES

pituitary gland, and that its release during pregnancy is also stimulated by human chorionic
gonadotrophin from the placenta. It remains unclear whether relaxin can feed back to the pituitary
or the foetus to affect luteinising hormone or human chorionic gonadotrophin levels and so control
its own release.

Relaxin carries out its actions on the reproductive system and other organs by activating specific
receptors on these tissues.

What happens if I have too much relaxin?

Disorders of relaxin secretion have not been described in detail. Studies have suggested that high
levels of circulating relaxin in the mother are associated with premature birth, presumably via its
effects on the rupture of the foetal membranes and the opening of the cervix. However, further
research is needed to confirm these findings.

What happens if I have too little relaxin?

There is some evidence that low levels of relaxin may contribute to a condition known as
scleroderma, where the skin thickens and hardens. This is caused by the development of fibrosis and
scarring on the skin, which also occurs in the lung, stomach and blood vessels.

75
 HORMONES

41. Somatostatin
Somatostatin is a hormone that inhibits the secretion of several other hormones, including growth
hormone, thyroid stimulating hormone, cholecystokinin and insulin.
Alternative names for somatostatin
SS, SST or SOM; growth hormone inhibitory hormone (GHIH); somatotropin release inhibiting
factor (SRIF); somatotropin release inhibiting hormone (SRIH)

What is somatostatin?
Somatostatin is a hormone produced by many tissues in the body, principally in the nervous and
digestive systems. It regulates a wide variety of physiological functions and inhibits the secretion of
other hormones, the activity of the gastrointestinal tract and the rapid reproduction of normal and
tumour cells. Somatostatin may also act as a neurotransmitter in the nervous system.

The hypothalamus is a region of the brain that regulates secretion of hormones from the pituitary
gland located below it. Somatostatin from the hypothalamus inhibits the pituitary gland’s secretion
of growth hormone and thyroid stimulating hormone.

In addition, somatostatin is produced in the pancreas and inhibits the secretion of other pancreatic
hormones such as insulin and glucagon. Somatostatin is also produced in the gastrointestinal tract
where it acts locally to reduce gastric secretion, gastrointestinal motility and to inhibit the secretion
of gastrointestinal hormones, including gastrin and secretin.

Chemically altered equivalents of somatostatin are used as a medical therapy to control too much
hormone secretion in patients with acromegaly and other endocrine conditions, and to treat some
gastrointestinal diseases and a variety of tumours.

How is somatostatin controlled?

In the same way that somatostatin controls the production of several hormones, these hormones
feed back to control the production of somatostatin. This is increased by raised levels of these other
hormones and reduced by low levels.

Somatostatin is also secreted by the pancreas in response to many factors related to food intake,
such as high blood levels of glucose and amino acids.

What happens if I have too much somatostatin?

Excessive somatostatin levels in the bloodstream may be caused by a rare endocrine tumour that
produces somatostatin, called a ‘somatostatinoma’. Too much somatostatin results in extreme
reduction in secretion of many endocrine hormones. An example of this is suppression of insulin
secretion from the pancreas leading to raised blood glucose levels (diabetes). As somatostatin
inhibits many functions of the gastrointestinal tract, its overproduction may also result in the
formation of gallstones, intolerance to fat in the diet and diarrhoea.

76
 HORMONES

What happens if I have too little somatostatin?

Since somatostatin regulates many physiological processes, too little somatostatin production would
lead to a variety of problems, including too much secretion of growth hormone. However, there are
very few reports of somatostatin deficiency.

77
 HORMONES

42. Testosterone
Testosterone is a hormone that is responsible for many of the physical characteristics specific to
adult males. It plays a key role in reproduction and the maintenance of bone and muscle strength.
Alternative names for testosterone
Testo (brand name for testosterone formulations); 4-androsten-17β-ol-3-one

What is testosterone?
Testosterone is produced by the gonads (by the Leydig cells in testes in men and by the ovaries in
women), although small quantities are also produced by the adrenal glands in both sexes. It is an
androgen, meaning that it stimulates the development of male characteristics.

Present in much greater levels in men than women, testosterone initiates the development of the
male internal and external reproductive organs during foetal development and is essential for the
production of sperm in adult life. This hormone also signals the body to make new blood cells,
ensures that muscles and bones stay strong during and after puberty and enhances libido both in
men and women. Testosterone is linked to many of the changes seen in boys during puberty
(including an increase in height, body and pubic hair growth, enlargement of the penis, testes and
prostate gland, and changes in sexual and aggressive behaviour). It also regulates the secretion of
luteinising hormone and follicle stimulating hormone. To effect these changes, testosterone is often
converted into another androgen called dihydrotestosterone.

In women, testosterone is produced by the ovaries and adrenal glands. The majority of testosterone
produced in the ovary is converted to the principle female sex hormone, oestradiol.

How is testosterone controlled?

The regulation of testosterone production is tightly controlled to maintain normal levels in blood,
although levels are usually highest in the morning and fall after that. The hypothalamus and the
pituitary gland are important in controlling the amount of testosterone produced by the testes. In
response to gonadotrophin-releasing hormone from the hypothalamus, the pituitary gland produces
luteinising hormone which travels in the bloodstream to the gonads and stimulates the production
and release of testosterone.

As blood levels of testosterone increase, this feeds back to suppress the production of
gonadotrophin-releasing hormone from the hypothalamus which, in turn, suppresses production of
luteinising hormone by the pituitary gland. Levels of testosterone begin to fall as a result, so
negative feedback decreases and the hypothalamus resumes secretion of gonadotrophin-releasing
hormone.

What happens if I have too much testosterone?

The effect excess testosterone has on the body depends on both age and sex. It is unlikely that adult
men will develop a disorder in which they produce too much testosterone and it is often difficult to
spot that an adult male has too much testosterone. More obviously, young children with too much

78
 HORMONES

testosterone may enter a false growth spurt and show signs of early puberty and young girls may
experience abnormal changes to their genitalia. In both males and females, too much testosterone
can lead to precocious puberty and result in infertility.

In women, high blood levels of testosterone may also be an indicator of polycystic ovary syndrome.
Women with this condition may notice increased acne, body and facial hair (called hirsutism),
balding at the front of the hairline, increased muscle bulk and a deepening voice.

There are also several conditions that cause the body to produce too much testosterone. These
include androgen resistance, congenital adrenal hyperplasia and ovarian cancer.

The use of anabolic steroids (manufactured androgenic hormones) can lead to a perceived high level
of testosterone by the hypothalamus, resulting in reduced luteinising hormone secretion from the
pituitary gland and, in turn, a decrease in the amount of testosterone produced within the testes,
while artificial testosterone levels remain high. In men, prolonged exposure to anabolic steroids
results in infertility, a decreased sex drive, shrinking of the testes and breast development. Liver
damage may result from its prolonged attempts to detoxify the anabolic steroids. Behavioural
changes (such as increased irritability) may also be observed. Undesirable reactions also occur in
women who take anabolic steroids regularly, as a high concentration of testosterone, either natural
or manufactured, can cause masculinisation (virilisation) of women.

What happens if I have too little testosterone?

If testosterone deficiency occurs during foetal development, then masculinisation of the foetus will
fail to occur normally and this may give rise to disorders of sex development. If testosterone
deficiency occurs during puberty, a boy’s growth may slow and no growth spurt will be seen. The
child may also fail to develop full sexual characteristics (hypogonadism) associated with men
undergoing puberty, including development of pubic hair, growth of the penis and testes and
deepening of the voice. Around the time of puberty, boys with too little testosterone may also have
less than normal strength and endurance, and their arms and legs may continue to grow out of
proportion with the rest of their body.

In adult men, low testosterone may lead to a reduction in muscle bulk, loss of body hair and a
wrinkled ‘parchment-like’ appearance of the skin. Testosterone levels in men decline naturally as
they age. In the media, this is sometimes referred to as the male menopause (andropause).

Low testosterone levels can cause mood disturbances, increased body fat, loss of muscle tone,
inadequate erections and poor sexual performance, osteoporosis, difficulty with concentration,
memory loss and sleep difficulties. Current research suggests that this effect occurs in only a small
group of ageing men. However, there is a lot of research currently in progress to find out more
about the effects of testosterone in older men and also whether the use of testosterone replacement
therapy would have any benefits.

79
 HORMONES

43. Thyroid stimulating hormone

Thyroid stimulating hormone is produced by the pituitary gland. Its role is to regulate the
production of hormones by the thyroid gland.
Alternative names for thyroid stimulating hormone
TSH; thyrotropin, thyrotrophin

What is thyroid stimulating hormone?

Thyroid stimulating hormone is produced and released into the bloodstream by the pituitary gland.
It controls production of the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland
by binding to receptors located on cells in the thyroid gland. Thyroxine and triiodothyronine are
essential to maintaining the body’s metabolic rate, heart and digestive functions, muscle control,
brain development and maintenance of bones.

How is thyroid stimulating hormone controlled?

When thyroid stimulating hormone binds to the receptor on the thyroid cells, this causes these cells
to produce thyroxine and triiodothyronine and release them into the bloodstream. These hormones
have a negative effect on the pituitary gland and stop the production of thyroid stimulating hormone
if the levels of thyroxine and triiodothyronine are too high. They also switch off production of a
hormone called thyrotropin-releasing hormone. This hormone is produced by the hypothalamus and
it also stimulates the pituitary gland to make thyroid stimulating hormone.

What happens if I have too much thyroid stimulating

hormone?
A simple blood test can measure thyroid stimulating hormone in the circulation. If a person has too
much, this may indicate that their thyroid gland is not making enough thyroid hormone, that is, they
have an underactive thyroid gland or hypothyroidism. People with an underactive thyroid often feel
lethargic, experience weight gain and feel the cold. Their thyroid gland may enlarge to produce a
goitre. Treatment is medication in the form of tablets to bring the level of thyroid hormones back to
normal. This also reduces the amount of thyroid stimulating hormone in circulation. It is
particularly important for pregnant women to have the correct amounts of thyroid stimulating
hormone and thyroid hormones to ensure the healthy development of their babies. Thyroid
stimulating hormone is one of the hormones measured in newborns.

What happens if I have too little thyroid stimulating

hormone?
If a person has too little thyroid stimulating hormone, it is most likely that their thyroid gland is
making too much thyroid hormone, that is, they have an overactive thyroid or hyperthyroidism,
which is suppressing the thyroid stimulating hormone. People with an overactive thyroid have the
opposite symptoms to those with hypothyroidism, i.e. they lose weight (despite increasing the
80
 HORMONES

amount they eat), feel too hot and can experience palpitations or anxiety. They may also have a
slightly enlarged thyroid gland. Treatment is medication in the form of tablets, which reduce the
activity of the thyroid gland and return all thyroid hormone levels to normal.

81
 HORMONES

44. Thyrotropin-releasing hormone

Thyrotropin-releasing hormone is produced by the hypothalamus. It plays an important role in the
regulation of thyroid gland activity.
Alternative names for thyrotropin-releasing hormone
Thyrotrophin-releasing hormone; TRH

What is thyrotropin-releasing hormone?

Thyrotropin-releasing hormone is one of the smallest hormones in the body, consisting of a
miniature chain of just three amino acid building blocks. It is made by a cluster of nerve cells in the
hypothalamus, an area at the base of the brain just above the pituitary gland. This nerve cell cluster
is known as the paraventricular nucleus. The nerve fibres that come out of it carry the thyrotropin-
releasing hormone and release it into the blood surrounding the pituitary gland, where it has its most
important action. This is to regulate the formation and secretion of thyroid stimulating hormone in
the pituitary gland, which in turn regulates the production of thyroid hormones in the thyroid gland.
Thyrotropin-releasing hormone is very short-lived, lasting for a matter of two minutes and
travelling less than an inch in the bloodstream to the pituitary gland before it is broken down.

Secretion of thyrotropin-releasing hormone by the hypothalamus can also stimulate the release of
another hormone from the pituitary gland, prolactin. Apart from its role in control of pituitary
thyroid stimulating hormone and prolactin release, thyrotropin-releasing hormone has a wider
distribution in tissues of the nervous system where it may act as a neurotransmitter. For instance, an
injection of thyrotropin-releasing hormone has effects on the arousal and feeding centres of the
brain, causing wakefulness and loss of appetite.

How is thyrotropin-releasing hormone controlled?

As its name implies, the main effect of thyrotropin-releasing hormone is to stimulate the release of
thyrotropin (also known as thyroid stimulating hormone) from the pituitary gland. Thyrotropin-
releasing hormone is the master regulator of thyroid gland growth and function (including the
secretion of the thyroid hormones thyroxine and triiodothyronine). These hormones control the
body’s metabolic rate, heat generation, neuromuscular function and heart rate, among other things.
If there is insufficient thyroid hormone available for the brain, this will be detected by the
hypothalamus and thyrotropin-releasing hormone will be released into the blood supplying the
pituitary gland. The effect of thyrotropin-releasing hormone on the pituitary gland is to trigger
thyroid stimulating hormone release, which stimulates the thyroid gland to make more thyroid
hormone. In summary, thyrotropin-releasing hormone is really the brain’s first messenger signal in
the many actions controlling thyroid hormone secretions.

Thyrotropin-releasing hormone in its pharmaceutical formulation of ‘protirelin’ used to be widely

used as a drug to test whether someone had thyroid overactivity. However, there are now more
sensitive measurements that can detect very low levels of thyroid stimulating hormone in the blood.
Thyrotropin-releasing hormone tests are still occasionally carried out but are normally used for the
diagnosis of conditions caused by resistance to thyroid hormone action.

82
 HORMONES

What happens if I have too much thyrotropin-releasing

hormone?
There is no known case of too much thyrotropin-releasing hormone.

What happens if I have too little thyrotropin-releasing

hormone?
If a person has too little thyrotropin-releasing hormone, they will develop thyroid underactivity
(hypothyroidism). This is a rare scenario in which a specific injury or tumour destroys this area of
the hypothalamus. This situation is referred to as secondary or central hypothyroidism.

83
 HORMONES

45. Thyroxine
Thyroxine is the main hormone secreted into the bloodstream by the thyroid gland. It plays vital
roles in digestion, heart and muscle function, brain development and maintenance of bones.
Alternative names for thyroxine
T4; tetraiodothyronine; thyroxin

What is thyroxine?
Thyroxine is the main hormone secreted into the bloodstream by the thyroid gland. It is the inactive
form and most of it is converted to an active form called triiodothyronine by organs such as the liver
and kidneys. Thyroid hormones play vital roles in regulating the body’s metabolic rate, heart and
digestive functions, muscle control, brain development and maintenance of bones.

How is thyroxine controlled?

The production and release of thyroid hormones, thyroxine and triiodothyronine, is controlled by a
feedback loop system that involves the hypothalamus in the brain and the pituitary and thyroid
glands. The hypothalamus secretes thyrotropin-releasing hormone which, in turn, stimulates the
pituitary gland to produce thyroid stimulating hormone. This hormone stimulates the production of
the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland.

This hormone production system is regulated by a negative feedback loop so that when the levels of
the thyroid hormones, thyroxine and triiodothyronine increase, they prevent the release of both
thyrotropin-releasing hormone and thyroid stimulating hormone. This system allows the body to
maintain a constant level of thyroid hormones in the body.

What happens if I have too much thyroxine?

The release of too much thyroxine in the bloodstream is known as thyrotoxicosis. This may be
caused by overactivity of the thyroid gland (hyperthyroidism), as in Graves’ disease, inflammation
of the thyroid or a benign tumour. Thyrotoxicosis can be recognised by a goitre, which is a swelling
of the neck due to enlargement of the thyroid gland. Other symptoms of thyrotoxicosis include
intolerance to heat, weight loss, increased appetite, increased bowel movements, irregular menstrual
cycle, rapid or irregular heartbeat, palpitations, tiredness, irritability, tremor, hair loss and retraction
of the eyelids resulting in a ‘staring’ appearance.

What happens if I have too little thyroxine?

Too little production of thyroxine by the thyroid gland is known as hypothyroidism. It may be
caused by autoimmune diseases, poor iodine intake or brought on by the use of certain drugs.
Sometimes, the cause is unknown. Thyroid hormones are essential for physical and mental
development so hypothyroidism during development or before birth and during childhood causes
mental impairment and reduced physical growth.

84
 HORMONES

Hypothyroidism in adults causes a decreased metabolic rate. This results in symptoms that include
fatigue, intolerance of cold temperatures, low heart rate, weight gain, reduced appetite, poor
memory, depression, stiffness of the muscles and infertility.

85
 HORMONES

46. Triiodothyronine
Triiodothyronine is a thyroid hormone that plays vital roles in the body’s metabolic rate, heart and
digestive functions, muscle control, brain development and the maintenance of bones.
Alternative names for triiodothyronine
T3

What is triiodothyronine?
Triiodothyronine is the active form of the thyroid hormone, thyroxine. Approximately 20% of
triiodothyronine is secreted into the bloodstream directly by the thyroid gland. The remaining 80%
is produced from conversion of thyroxine by organs such as the liver and kidneys. Thyroid
hormones play vital roles in regulating the body’s metabolic rate, heart and digestive functions,
muscle control, brain development and the maintenance of bones.

How is triiodothyronine controlled?

The production and release of thyroid hormones, thyroxine and triiodothyronine, is controlled by a
feedback system involving the hypothalamus, pituitary gland and thyroid gland. Activation of
thyroid hormones is then controlled in body tissues such as the liver, brain and kidneys by enzymes
called deiodinases which convert thyroxine into the active form triiodothyronine. Most of the
body’s circulating triiodothyronine (about 80%) is produced in this way.

The thyroid hormone production system is regulated by a negative feedback loop so that when the
levels of the thyroid hormones thyroxine and triiodothyronine increase, they prevent the release of
both thyrotropin-releasing hormone from the hypothalamus and thyroid stimulating hormone from
the pituitary gland. This system allows the body to maintain a constant level of thyroid hormones in
the body.

What happens if I have too much triiodothyronine?

Thyrotoxicosis is the name of the condition in which people have too much thyroid hormone in
their bloodstreams. It may result from overactivity of the thyroid gland (hyperthyroidism) from
conditions such as Graves’ disease, inflammation of the thyroid or a benign tumour. Thyrotoxicosis
may be recognised by a goitre, which is a swelling of the neck due to enlargement of the thyroid.
Other symptoms of thyrotoxicosis include heat intolerance, weight loss, increased appetite,
increased bowel movements, irregular menstrual cycle, rapid or irregular heartbeat, palpitations,
tiredness, irritability, tremor, hair loss and retraction of the eyelids, which results in a ‘staring’
appearance.

What happens if I have too little triiodothyronine?

Hypothyroidism is the term for the production of too little thyroid hormone by the thyroid gland.
This may be because of autoimmune diseases, poor iodine intake or the result of taking particular
drugs. Since thyroid hormones are essential for physical and mental development, hypothyroidism
before birth and during childhood results in learning disability and reduced physical growth.
86
 HORMONES

Hypothyroidism in adults results in a slowing of the body’s functions with symptoms such as
tiredness, intolerance to cold temperatures, low heart rate, weight gain, reduced appetite, poor
memory, depression, stiffness of the muscles and infertility.

87
 HORMONES

47. Vitamin D
Vitamin D is a hormone produced by the kidneys that helps to control the concentration of calcium
in the blood and is vital for the development of strong bones.
Alternative names for vitamin D
Calcitriol (or 1,25-dihydroxyvitamin D); ergocalciferol (vitamin D ) cholecalciferol (vitamin D );
2 ; 3

calcidiol (25-hydroxyvitamin D)

What is vitamin D?
Vitamin D is actually a hormone rather than a vitamin. The body makes most of the vitamin D it
needs; only about 10% comes from our food. The action of sunlight on our skin produces a
substance called cholecalciferol, which is converted by the liver to calcidiol. This is further
converted in the kidneys by the enzyme 1α-hydroxylase to calcitriol, the active form of vitamin D.
Calcidiol is considered a good indicator of vitamin D levels and is the form that is usually measured
by doctors.

The active form of vitamin D is produced primarily by the kidneys, but there are also a number of
other tissues in the body that activate vitamin D. Excess cholecalciferol and calcidiol made during
the summer are stored in our fat for use during the winter. Vitamin D modifies the activity of bone
cells and is important for the formation of new bone in children and adults. It also regulates calcium
levels in the blood by helping the body to absorb calcium from food and by preventing calcium loss
from the kidneys. Recently, the role of vitamin D as a potent regulator of other functions throughout
the body has emerged, although we are only just beginning to fully understand what these are and
the significance for our health.

How is vitamin D controlled?

A fall in the concentration of calcium in the bloodstream is detected by the parathyroid glands,
which then produce parathyroid hormone. Parathyroid hormone increases the activity of the enzyme
1α-hydroxylase, which produces active vitamin D. This increase in the concentration of calcium
together with vitamin D feeds back to the parathyroid glands to stop further parathyroid hormone
release. The production of vitamin D is also directly regulated by calcium, phosphate and calcitriol.

What happens if I have too little vitamin D?

Vitamin D deficiency is common in the UK, probably due to lifestyle changes and increased
concern about sun exposure. If you have too little vitamin D you are unable to maintain an adequate
concentration of calcium in your blood for bone growth. This causes rickets in children and
osteomalacia in adults. As the role of vitamin D as a regulator of other functions throughout the
body has emerged, it has been suggested that a lack of vitamin D is linked to an inability to fight
infections effectively, the development of diabetes, certain cancers, multiple sclerosis, depression,
heart disease, high blood pressure, and stroke, although the direct relevance and mechanisms
underlying these responses remain unknown.

What happens if I have too much vitamin D?

88
 HORMONES

It is very rare to have too much vitamin D. If you have too much vitamin D the level of calcium in
your blood may increase and this causes a condition known as hypercalcaemia, which can cause a
number of symptoms such as nausea, vomiting, constipation, tiredness, confusion, depression,
headaches, muscle weakness, the need to pass urine more frequently and feeling thirsty. However,
this condition is very rare.

89