HYPOTHALAMUS- PITUITARY AXIS

Adila A Hamid
Department of Physiology
PPUKM
adilahamid@ppukm.ukm.edu.my
Objectives :

◦ Explain the endocrine function of hypothalamus

◦ Explain relationship between hypothalamus & pituitary
◦ Discuss regulation of anterior pituitary hormonal secretions
◦ Discuss regulation of posterior pituitary hormonal secretions &
their actions
The endocrine system consists of
the ductless endocrine glands
scattered throughout the body

Endocrine gland

Secrete hormones into the blood

Hormones travels in the blood to

its distant target cells

Regulates/directs particular
functions
 Major regulatory systems of our
body

Nervous system Endocrine system

 Coordinates rapid, precise  Controls activities that require

responses duration rather than speed

 Important in mediating the  Regulates, coordinates,

body’s interaction with the integrates cellular and organ
external environment function
 Functions of endocrine system

Regulate nutrient Inducing adaptive Promoting growth & Controllling

metabolism & H2O changes to help the development reproduction
and electrolyte body cope with stress
imbalance

Regulating RBC
Controlling integrating
activities of circulatory
and digestive systems
 Dealing with stress……….

Hypothalamus (receives stress Releases corticotropin releasing hormone (CRH)

information)
stimulates

Anterior pituitaty to secrete adrenocorticotropic

hormone (ACTH)
Increase glucose levels, glycerol and
fatty acids stimulates
Increase heart rate
Increase breathing rate
Adrenal medulla to secrete cortisol
Redirects blood from skin & internal
organs to the skeletal muscle
Posterior pituitary secretes ADH for the Cortisol supplies body with amino acids and extra
body to hang on to sodium and water energy source to repair any injured tissues
Preparing the body for fight or
Anterior pituitary secretes GH to prepare
flight action / immediate physical
energy sources
action
Endocrine is a complex system because …….

 A single endocrine gland may produce multiple hormones.

 Anterior pituitary secrete 6 different hormones

 A single hormone may be secreted by more than one endocrine gland

 hypothalamus & pancreas secrete somatostatin

 A single hormone can have more than one type of target cell
 Vasopressin promotes H2O absorption by the kidney tubule
 Vasopressin causes vasoconstriction of arteriolar smooth muscle

 Rate of secretion varies over the course of time.

 Endocrine control in reproductive cycles
 Tropic hormones (tropic = “nourishing)

 Hormones that regulate the production of another hormone

 Example :
stimulates
Thyroid-stimulating hormone (TSH) thyroid gland to secrete thyroid hormone

structural integrity of thyroid gland

Thyroid-stimulating hormone (TSH) Low levels of thyroid

hormone

Thyroid gland shrinks

 Hypothalamus

◦ A collection of specific nuclei and associated fibers that lie beneath

the thalamus
◦ An important link between the autonomic nervous system and the
endocrine system

Functions :
(1) Controls body temperature
(2) Controls thirst and urine output
(3) Controls food intake
(4) Controls anterior pituitary hormone secretions
(5) Produces posterior pituitary hormones
(6) Controls uterine contractions and milk ejection
(7) Serve as major autonomic nervous system coordinating centre,
which in turn affects all smooth muscle, cardiac muscle, and
exocrine glands
(8) Plays a role in emotional behavioral patterns
(9) Participates in the sleep-wake cycle
Hypothalamus & Pituitary

◦ Pituitary gland or hypophysis – a small endocrine gland

located in the bony cavity at the base of the brain just
below hypothalamus.

◦ Pituitary is connected to the hypothalamus by a thin

connecting stalk

◦ Pituitary gland
◦ anterior pituitary –consists of glandular epithelial tissue
(adenophypophysis)
◦ posterior pituitary – composed of nervous tissue
(neurophypophysis)

o The release of hormones of both anterior and posterior

pituitary is directly controlled by the hypothalamus
 Hypothalamic-releasing-
inhibiting hormones (e.g
TRH)

Hypothalamus-hypophysial
portal vessels.

Posterior lobe hormones

(e.g ADH)

Hypothalamus-hypophysial
portal vessels.

Target tissues (e.g kidney) Target tissues (e.g thyroid)

 Major Hypophysiotropic Hormones
(Hypophysis = pituitary, tropic= nourishing)

Hormone Effect on the Anterior Pituitary

Thyrotropin releasing- hormone (TRH) Stimulates release of TSH (thyrotropin) and prolactin

Gonadotropin-releasing-hormone (GnRH) Stimulate release of FSH & LH (gonadotropins)

Corticotropin-releasing hormone (CRH) Stimulate release of ACTH (corticotropin)

Growth hormone-releasing hormone (GHRH) Stimulate release of growth hormone

Growth hormone-inhibiting hormone (GHIH) Inhibits release of growth hormone and TSH
/Somatostatin

Prolactin-releasing hormone Stimulate release of prolactin

Prolactin-inhibiting hormone Inhibits release of prolactin

(PIH)/dopamine

* These hormones is synthesized in the cell bodies of hypothalamic neurons and acts on the cells of
anterior pituitary
Relationship between anterior pituitary and hypothalamus
1. Hypophysiotropic hormones produced by
neurosecretory neurons in the hypothalamus enter
the hypothalamic capillaries

2. Hypothalamic capillaries rejoin to form

hypothalamic-hypophyseal portal system (a
vascular link to anterior pituitary

3. The portal system branches into capillaries of the

AP

4. Hypophysiotropic hormones leave the blood

across the AP capillaries, control the release of AP
hormones

5. When stimulated by the appropriate hypothalamic

releasing hormone, the AP secretes a given
hormone into these capillaries

6. AP capillaries rejoin to form a vein through which

the AP hormone leave for ultimate distribution
throughout the body
 Anterior Pituitary

 Unlike posterior pituitary which releases hormones synthesizes by the

hypothalamus, anterior pituitary itself synthesizes the hormones it releases into the
blood

 Secretes 6 major peptide hormones (TSH, FSH, LH, ACTH, GH, PRL)

5 different cell population secrete 6 major peptide hormones

 Somatotropes secrete growth hormone ( GH, somatotropin)
 Thyrotropes secrete thyroid-stimulating hormone (TSH, throtopin)
 Corticotropes produce and release adrenocorticotropic hormone (CTH, adrenocorticotropin)
 Gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
 Lactotropes secrete prolactin (PRL)
 Anterior Pituitary

◦ Most AP hormones are ‘tropic’ (means: ‘feed’) hormones because they each
regulate secretion of another specific endocrine glands.
 FSH & LH (Gonadotropins) – they control secretion of the sex hormones by the gonad
 GH exerts its growth-promoting effects indirectly by stimulating the release of IGF-1 by the liver

◦ Exception: Prolactin is not a tropic hormone as it does not stimulate secretion of

another hormone. It acts directly on nonendocrine tissue to exert its effects
 Prolactin acts on mammary glands for breast growth and milk secretion
 Regulation of anterior pituitary hormonal secretion

(1) Hypothalamic hormones

o Hormones release by the hypothalamus to stimulate/inhibit AP hormones secretion
o Example: Thyrotropin-releasing hormone (hypothalamic-releasing hormone) stimulate
thyrotroph in the anterior pituitary gland to secrete thyroid stimulating hormone

(2) Feedback mechanism

(1) Negative feedback mechanism ( Hormonal inhibition of hormone release)
Long loop negative feedback
Short loop negative feedback
(2) Positive feedback mechanism
Regulation of hormone secretion : Negative feedback mechanism

 Some features of hormone action, direct or

indirectly, inhibits further secretion of the
hormone

 Long-loop negative feedback

Hormones feed back all the way to hypothalamic-
pituitary axis (either hypothalamus &/or AP)

 Short-loop negative feedback

AP hormone feeds back on the hypothalamus to inhibit
secretion of hypothalamic-releasing hormone

What are other examples of negative feedback

mechanism in our body ?
 Negative feedback mechanism: Regulation of cortisol secretion
Stress
(injury, fasting, surgery, final exams)
1. Stress induces the hypothalamus to
release corticotropin releasing hormone
+ (CRH) into the portal vein.

- Hypothalamus - 2. CRH binds to receptors on corticotrophs

in the anterior pituitary, and stimulates the

Short -loop feedback

release of adrenocorticotropic hormone
CRH (ACTH)
Long-loop feedback

+ 3. ACTH travels through the blood stream to

the adrenal cortex, and increases
- Anterior Pituitary
synthesis and release of cortisol.

4. Cortisol travels through bloodstream back

to the hypothalamus and pituitary to exert
ACTH negative feedback on CRH and ACTH

Adrenal cortex
Increase blood glucose
Metabolic fuels and building
Increase blood amnio acids blocks available to help resist
Cortisol stress
Increase blood fatty acids
Negative feedback mechanism: Regulation of thyroid secretion
 Positive feedback mechanism
FSH and LH secretion during follicular phase of menstrual cycle

Hypothalamus 1. Hypothalamus release gonadotropin hormone (GnRH) into

the portal vein.

GnRH 2. GnRH binds to receptors on gonadotrophs in the anterior

pituitary, and stimulates the release of Follicule stimulating
+ hormone (FSH) & leutinizing hormone (LH)
+
3. FSH & LH travels through the blood stream to the ovary to
Anterior Pituitary start the development of the follicle, and increases estrogen
secretion

4. Increased amount of estrogen at the follicular phase of

FSH, LH menstrual cycle causes a positive feedback on LH cells in
+ the pituitary

5. LH secretion will rise and ovulation occurs

Ovary Estradiol
 Posterior Pituitary

 The hypothalamus and posterior pituitary form

a neuroendocrine system that consists of a
population of neurosecretory neurons,
supraoptic nucleus and the paraventricular
nucleus.

 Posterior pituitary is an extension of the

hypothalamus

Posterior pituitary does not produce any

hormones. It simply stores and on appropriate
stimulation, releases into the blood two small
peptide hormones, vasopressin (ADH) and
oxytocin, which are synthesized by the
neuronal cell bodies in hypothalamus
Relationship between posterior pituitary and hypothalamus

1. The paraventricular and supraoptic nuclei both

contain neurons that produce vasopressin or
oxytocin depending on the neurons, is synthesized
in the neuronal cell body in the hypothalamus

2. The hormones travels down the axon to be stored

in the neuronal terminals within the posterior
pituitary

3. When the neurons is excited, the stored hormone

is released from the terminals into the systemic
blood for distribution throughout the body.

* ADH is associated with supraoptic nuclei

* Oxytocin is associated with paraventricular nucleus
increase water increase total
reabsorption peripheral
resistance
 Control of oxytocin release during parturition

3 The hypothalamus stimulate

oxytocin secretion from posterior
2 pituitary
The fetus’s head pushing against
cervix stimulates stretch receptor
that sends signals to mother’s
hypothalamus

1
Estrogen from placenta readies
the uterus for a response to
oxytocin

Prostaglandins Oxytocins

Oxytocin stimulate
Prostaglandin secreted by the uterus also stronger uterine
enhance contractions. contraction 4
5
* The contractile activity of the uterus acts through
feedback mechanisms during parturition to stimulate oxytocin,
and this further increases the secretion of oxytocin.
Physiology of lactation
Regulation of vasopression (ADH) secretion
Q1: Which of these is not secreted from the anterior pituitary?
a) Thyroid stimulating hormone c) Oxytocin
b) Follicular Stimulating Hormone d) Lutenising Hormone

Q2: Which of the following affect secretion of prolaction

a) Dopamine c) GnRH analogue
b) FSH d) Serotonin

Q3: Excess prolactin causes

a) Acromegaly c) Anaemia
b) Gynaecomastia d) Early menopause

Q4 : Hormones produced by anterior pituitary that have direct effect on the body, rather than triggering another gland, are
a) GH, prolactin c) Testosterone and oestrogen
b) TSH, ACTH and gonadotropic hormones d) Progestrone

Q5: Hypothalamic releasing and release-inhibiting hormones are transported from the hypothalamus to the anterior pituitary by
way of
a) The general bloodstream c) Direct contact between the two organs
b) A portal system of blood vessels directly connecting the two d) a cascade of release-inhibit-release interactions
organs
Q6: Which of the following hormones may also be referred to as neurohormones?
a) Thyroid stimulating hormone c) Prolactin
b) ADH d) Aldosterone

Q7: All the following are true about posterior hormones EXCEPT:
a) They include antidiuretic hormone & oxytocin c) They are synthesized in the posterior pituitary
b) They include tropic hormones d) A nerve signal from the hypothalamus stimulates their release

Q8: Which of the following is a physiological function that is mediated by a hormone released by the posterior pituitary
a) Maturation of the egg and sperm c) Increase in thyroid hormone level
b) Water retention d) Decrease in calcium level

Q9 : All the following are true for ADH except?

a) Acts on distal tubule and increase water permeability c) Neurosecretion
b) Increased secretion when plama osmolarity is low d) Causes arteriolar contraction
Endocrine gland Hormones Target cells Major functions of Hormones
Anterior Pituitary Thyroid follicular cells Stimulates T3 and T4 secretion

ACTH Zona fasciculate and zona reticularis of the adrenal

cortex
Bone and soft tissue Stimulates IGF-1 to stimulate protein anabolism
and growth of bones and soft tissues,
Direct metabolic effects include mobilizing fat and
conserving glucose

Liver

Females : Ovarian follicles Promotes follicular growth and development;

stimulates estrogen secretion
Males : Seminiferous tubules in testes

LH Females : Ovarian follicle and corpus luteum Stimulates ovulation, corpus luteum development
and estrogen & progesterone secretion
Males: Interstitial cells of Leydig in testes Stimulates sperm production

Prolactin Mammary Gland

Posterior Pituitary Vasoppresin Increases water reabsorption

(ADH)
Arterioles

Oxytocin Increases contractility

Mammary Glands (breasts)