Hypothalamo-Hypophiseal

System
 (a) Humoral: in response to changing
Mechanisms levels of ions or nutrients in the blood
of hormone (b) Neural: stimulation by nerves
(c) Hormonal: stimulation received from
release other hormones

2
 The pituitary gland (hypophysis) : is a small gland—about
1 cm in diameter and 0.5 to 1 gram in weight— that lies in
the sella turcica, a bony cavity at the base of the brain, and is
connected to the hypothalamus by the pituitary (or
hypophysial) stalk.

 the pituitary gland is divisible into two distinct portions: the

anterior pituitary, also known as the adenohypophysis, and
the posterior pituitary, also known as the
neurohypophysis.

 Embryologically, the two portions of the pituitary originate from

different sources—the anterior pituitary from Rathke’s pouch,
which is an embryonic invagination of the pharyngeal
epithelium, and the posterior pituitary from a neural tissue
outgrowth from the hypothalamus..
5
6
HYPOTHALAMUS CONTROLS
PITUITARY SECRETION

 Almost all secretion by the pituitary is controlled by

either hormonal or nervous signals from the
hypothalamus.
 Secretion from the posterior pituitary is controlled
by nerve signals that originate in the hypothalamus
and terminate in the posterior pituitary.
 secretion by the anterior pituitary is controlled by
hormones called hypothalamic releasing and
hypothalamic inhibitory hormones (or factors)
secreted within the hypothalamus itself and then
conducted, to the anterior pituitary through minute
blood vessels called hypothalamic-hypophysial
portal vessels.
 The hypothalamus receives signals from many
sources in the nervous system.
 Thus, the hypothalamus is a collecting center for
information concerning the internal well-being of the
body, and much of this information is used to
control secretions of the many globally important
pituitary hormones.
 Special neurons in the hypothalamus synthesize
and secrete the hypothalamic releasing and
inhibitory hormones into the median eminence that
control secretion of the anterior pituitary
hormones
.

 The endings of these fibers are different from most

endings in the central nervous system, in that
their function is not to transmit signals from one
neuron to another but rather to secrete the
hypothalamic releasing and inhibitory hormones
into the tissue fluids. These hormones are
immediately absorbed into the hypothalamic-
hypophysial portal system and carried directly to
the sinuses of the anterior pituitary gland.
 CELLS OF ANTERIOR
PITUITARY

 five cell types can be differentiated :

 1. Somatotropes—human growth hormone (hGH)

40- 50% of A.P cells .
 2. Corticotropes—adrenocorticotropin (ACTH) – 15-20% of A.P cells .
 3. Thyrotropes—thyroid-stimulating hormone
(TSH) 3-10% of A.P cells
 4. Gonadotropes—gonadotropic hormones, which
include both luteinizing
hormone (LH) and folliclestimulatinghormone
(FSH)
10-15% of A.P cells
 5. Lactotropes—prolactin (PRL) – 10-25% of A.P
cells .
Hypothalamic Releasing and Inhibitory Hormones Control Anterior
Pituitary Secretion

Hormone Primary Action on Anterior Pituitary

Thyrotropin-releasing hormone (TRH) Stimulates secretion of TSH by

thyrotropes

Gonadotropin-releasing hormone Stimulates secretion of FSH and LH by

(GnRH) gonadotropes

Corticotropin-releasing hormone (CRH) Stimulates secretion of ACTH by

corticotropes

Growth hormone–releasing hormone Stimulates secretion of growth

(GHRH) hormone by somatotropes

Growth hormone inhibitory hormone Inhibits secretion of growth hormone by

(somatostatin) somatotropes

Prolactin-inhibiting hormone (PIH) Inhibits secretion of prolactin by

lactotropes
PHYSIOLOGICAL FUNCTIONS OF GROWTH
HORMONE
 All the major anterior pituitary hormones, except for
growth hormone, exert their principal effects by
stimulating target glands, including thyroid gland,
adrenal cortex, ovaries, testicles, and mammary
glands.

 Growth hormone, in contrast to other hormones,

does not function through a target gland but exerts
its effects directly on all or almost all tissues of the
body.
 Growth hormone, also called somatotropic hormone
or somatotropin, is a small protein molecule that
contains 191 amino acids in a single chain.

 It causes growth of almost all tissues of the

body that are capable of growing. It promotes
increased sizes of the cells and increased
mitosis, with development of greater numbers of
cells and specific differentiation of certain types of
cells such as bone growth cells and early muscle
cells.
GROWTH HORMONE HAS
SEVERAL METABOLIC EFFECTS
(1) increased rate of protein synthesis in most cells
of the body.
(2) increased mobilization of fatty acids from adipose
tissue, increased free fatty acids in the blood,
and increased use of fatty acids for energy.
(3) decreased rate of glucose utilization
throughout the body. Thus, in effect, growth
hormone enhances body protein, uses up fat
stores, and conserves carbohydrates.
Growth Hormone Promotes Protein Deposition
:
in Tissues
A- Enhancement of Amino Acid Transport Through the
Cell Membranes :
 Growth hormone directly enhances transport of most of
amino acids through the cell membranes to the interior
of the cells. This increases the amino acid
concentrations in the cells and is responsible for the
increased protein synthesis.
B-Enhancement of RNA Translation to Cause Protein Synthesis
by the Ribosomes :
 Even when the amino acid concentrations are not
increased in the cells, growth hormone still increases
RNA translation, causing protein to be synthesized
in greater amounts by the ribosomes in the
cytoplasm.
 C -Increased Nuclear Transcription of DNA to Form RNA

 Over more prolonged periods (24 to 48 hours),

growth hormone also stimulates the transcription of
DNA in the nucleus, causing the formation of
increased quantities of RNA. This promotes more
protein synthesis and promotes growth.

 In the long run, this may be the most important

function of growth hormone.

D- Decreased Catabolism of Protein and Amino Acids.

“KETOGENIC” EFFECT OF
GROWTH HORMONE
 GH causes release of fatty acids from adipose tissue
and, therefore, increasing the concentration of fatty
acids in the body fluids.

 increase in lean body mass

 large quantities of acetoacetic acid are formed by the

liver and released into the body fluids, thus causing
ketosis.

 fatty liver
GROWTH HORMONE
DECREASES CARBOHYDRATE
UTILIZATION
 Growth hormone causes multiple effects that
influence carbohydrate metabolism, including :

(1) decreased glucose uptake in tissues such as

skeletal muscle and fat .
(2) increased glucose production by the liver,
(3) increased insulin secretion.
 Growth hormone–induced “insulin resistance,” which
decreases insulin’s actions to stimulate the uptake
and utilization of glucose in skeletal muscle and fat and
to inhibit gluconeogenesis by the liver;

 this leads to increased blood glucose concentration and

a compensatory increase in insulin secretion.

 For these reasons, growth hormone’s effects are called

diabetogenic, and excess secretion of growth hormone
can produce metabolic disturbances very similar to
those found in patients with type II (non-
insulindependent) diabetes, who are also very
resistant to the metabolic effects of insulin.
GROWTH HORMONE STIMULATES CARTILAGE
AND
BONE GROWTH
 growth hormone has an obvious effect on the
growth of skeletal frame including :
I. increased deposition of protein by the
chondrocytic and osteogenic cells that cause
bone growth.
II. increased rate of reproduction of these cells.
REGULATION OF GH SECRETION

 After adolescence, secretion decreases slowly with

aging – pulsatile - increases during the first 2 hours of
deep sleep.
HYPOTHALAMIC-CONTROL
 Growth hormone–releasing hormone (GHRH)

 growth hormone inhibitory hormone (also called

somatostatin)
REGULATION OF GROWTH
HORMONE SECRETION
ABNORMALITIES OF GROWTH HORMONE
SECRETION
 Panhypopituitarism - decreased secretion of all the
anterior pituitary hormones – congenital - pituitary tumor.

 Dwarfism –generalized deficiency of anterior pituitary

secretion (panhypopituitarism) during childhood.
- rate of development decreased – not pass through
puberty and never secretes sufficient quantities of
gonadotropic hormones to develop adult sexual
functions.

 Only GH is deficient - mature sexually and occasionally

reproduce
 Rx – human GH – synthesized by E. coli bacteria
as a result of recombinant DNA technology.

 Dwarfs who have pure growth hormone deficiency

can be completely cured if treated early in life.
 Panhypopituitarism in the Adult
craniopharyngiomas or chromophobe tumors, may
compress the pituitary gland .

 thrombosis of the pituitary blood vessels - when a new

mother develops circulatory shock after the birth of
her baby .

 The general effects :

(1)hypothyroidism,
(2)depressed production of glucocorticoids
(3)suppressed secretion of the gonadotropic hormones so
that sexual functions are lost.

 Lethargic person - lack of thyroid hormones

 Weight gain - lack of fat by growth,
mobilization adrenocorticotropic and
thyroid hormones
 In people who have lost the ability to secrete growth
hormone, some features of the aging process
accelerate.

 a 50-year-old person who has been without GH for

many years may have the appearance of a person
aged 65

 decreased protein deposition in most tissues of

the body - increased fat deposition - increased
wrinkling of the skin, diminished rates of function
of some of the organs, and diminished muscle
mass and strength
 Gigantism – Before puberty - acidophilic
tumors
in the gland - All body tissues grow rapidly
 8 feet giant – hyperglycemia – DM - death in early
adulthood
 Rx - microsurgical removal of the tumor or
by
irradiation of the pituitary gland
 Acromegaly – after puberty - cannot grow taller, but
the bones can become thicker and the soft tissues
can continue to grow.

 bones of the hands and feet - membranous bones,

including the cranium, nose, superiors on the
forehead, supraorbital ridges, lower jaw bone,
vertebrae.
A 12 year old boy, 6’5”, with his mother, and his hand (left)
in comparison with that of a grown man, 6’1”
All long bones in the body effected before closure of
epiphyseal growth plates
 lower jaw protrudes forward - the forehead slopes
forward – the nose increases twice normal size - the
feet require size 14 or larger shoes - the fingers
thickened - the hands are twice normal size - Vertebrae
bent back, – large tongue - liver, kidneys, enlarged
Medical Side Effects

 Life span is generally reduced

significantly due to medical
complications, ex. heart failure,
respiratory problems and
skeletal/muscular problems
 Tall stature, enlarged hands/feet,
coarse facial features, excessive
sweating, osteoarthritis, carpel tunnel
syndrome, cardiovascular diseases,
benign tumor growth, diabetes,
varying levels of obesity and sleep
apnea, deepening of voice
 Tumor in pituitary can cause chronic
headache and visual impairment due
to proximity of gland to optic chiasm
Testing and Diagnosis

 Not a heritable genetic

disorder, no prenatal
testing
 Initially growth is not
necessarily exaggerated;
with time becomes much
more apparent
 Blood work possible to
test circulating levels of
GH and IGF1
 Computed tomography
and magnetic resonance
imaging available to look
for pituitary tumors
Treatment
 Disorder is developmental in nature;
treatment difficult because GH continually
surges from pituitary, increasing body size
 Pituitary tumor (adenoma) can be removed
with surgery depending on its size to stop
release of GH
 Drugs: octreotide (somatostatine analog)

Dopamine agonists: Cabergoline

 Radiation can be used to treat tumor
 Stereotactic Gama Knife
 GH receptor antagonist (Pegvisomant)
Living with Gigantism

 Gigantism and acromegaly generally have

outward negative effects that can be treated
medically, i.e. sleep disturbances, joint pain,
cardiovascular issues, etc.
 Surgery is oftentimes ineffective due to
complex nature of endocrine system, very
stressful – gigantism very traumatic emotionally
 Causes general tiredness, muscular weakness,
impotence
 Generally, life with gigantism becomes more
difficult, however, several famous cases exist to
demonstrate possibility of more positive,
happier life
Robert Pershing Wadlow

 Robert Wadlow – “The

Alton Giant”
 Tallest man ever at

8’11”, suffered from the

disorder
 Born normal weight and

size but 30lbs at 6

months of age
Andre The Giant

 7’4”, 500lbs
 Wrestled in WWF and many
other leagues, won multiple
titles including heavy weight
and tag team belts
 Offered position on
Redskins, turned it down to
wrestle
 Had a role in The Princess
Bride as a giant
 Disabled later in life due to
joint pains and
cardiovascular complications
Andre the Giant

 Broke ankle stepping out

of bed, confined to wheel
chair when not in front of
camera
 Died in 1993 by
congestive heart failure in
his sleep
 Autopsy showed his heart
was abnormally large –
size of two fists
 Case study
 18 years old lady
 Height 180 cm
 Diagnosed in 2008 (at the age of 16)
 Acromegaly with Hyperprolactinemia
History
 From 6 years age taller than friends
 Slept for long periods up to 20 hrs at a time
 Headaches and tiredness
 Pins and needles in arms and hands.
 16 years went to GP referred to local hospital
 Diagnosed acromegaly, commenced

cabergoline
 Commenced menstrual periods.
History (12 months after referred to a new hospital
)

 Assessment (on cabergoline)

• IGF-I 109 nmol/l (ref. range 21-75.9 )
• Prolactin 129 mU/L (50 - 400)
• Non-suppression of GH during OGTT
• MRI scan macroadenoma
• Confirmed Acromegaly with
Hyperprolactinemia
Case Study
 2010 referred for surgery, had 2
transsphenoidal operations, not cured.

 Had Octreotide LAR injections, not controlled

 2011 referred to another hospital for further

opinion.
Case study
 Assessment (off cabergoline)
• IGF-I 790 mg/l (ref. range 151-528 )
• Prolactin 1810 mU/L (50 - 400)

• Persistent Acromegaly
• Thyroid and Cortisol defficient
• Diabetes Insipidus
• Menstrual periods stopped
Case Study
 Medication
 Thyroxin 75mkgs daily
 Hydrocortisone 10 mg
 Desmopresin spray
 Cabergolin
 Omeprazole
Case Study
 Cabergoline effective in 30 % patients

 Prolactin and GH co-secreting tumors

respond well to dopamine agonists.
• Biocemical response
• Tumor shrinkage
 Non-responsive to somatostatin analogues
 She now feels well on 3.5 mg cabergoline

weekly.
POSTERIOR PITUITARY GLAND AND
ITS RELATION TO THE
HYPOTHALAMUS
 Posterior pituitary gland =
neurohypophysis

 Composed of glial-like cells ( pituicytes) .

 Pituicyte do not secret hormones ( supporting

structure for terminal nerve fibers )

 Origin of these tracts : supraoptic and

paraventricular nuclei of the hypothalamus .
 These endings lie on the surfaces of capillaries,
where they secrete two posterior pituitary
hormones: (1) antidiuretic hormone (ADH), also
called vasopressin, and (2) oxytocin.

 These hormones are synthesized in hypothalamic

nuclei (cell bodies ) and packaged in secretory
granules with their respective neurophysins .

 Neurophysins : carrier protein .

 ADH is formed primarily in the supraoptic nuclei,
whereas oxytocin is formed primarily in the
paraventricular nuclei. Each of these nuclei can
synthesize about one sixth as much of the second
hormone as of its primary hormone.
CHEMICAL STRUCTURES OF ADH AND
OXYTOCIN

 Both oxytocin and ADH (vasopressin) are

polypeptides, each containing nine amino acids.
Their amino acid sequences are the following:
 these two hormones are almost identical except
that in vasopressin, phenylalanine and arginine
replace isoleucine and leucine of the oxytocin
molecule.
 The similarity of the molecules explains their partial
functional similarities.
ANTIDIURETICHORMONE
( VASOPRESSIN )
 acts on the collecting ducts of the kidney to facilitate
the reabsorption of water into the blood ( increase its
permeability) . This it acts to reduce the volume of urine
formed - very concentrated urine- .

 Amount of ADH secretion varies

with : Blood pressure & blood volume
.

 Target tissues :
 Kidneys
 Sweat glands
 Smooth muscle in blood vessel wall .
 High blood osmotic pressure ( or decreased blood
volume ) stimulate osmoreceptors , which
activate the supraoptic nuclei that synthesize and
release ADH .
 Low blood osmotic pressure ( or increased blood
volume ) inhibits the osmoreceptors which reduce
or stops ADH secretion .

** Osmoreceptors : are modified neuron receptors in

or near the hypothalamus , that monitor blood
osmotic pressure .
 High concentrations of ADH have a potent effect of
constricting the arterioles throughout the body and
therefore increasing the arterial pressure. For this
reason, ADH has another name, vasopressin.
OXYT
OCIN
 During and after delivery of a baby , oxytocin
affects two target tissues :
the mothers uterus and breasts .

 Oxytocin causes:-

 uterine contractions in labor.

 Milk letdown in lactating mothers .

 ** milk ejection
mechanism
Suckling signals Release of oxytocin by Post. pituitary
Hypothalamus
stimulus

Contraction of Milk
By blood to Less than a minute
Breast Myoepithelial cells begins to
( alveoli of flow
the mammary
glands )
DIABETIS INSIPIDUS

 Defects in antidiuretic hormone receptors or

inability to secret ADH .
 Neurogenic D.I results  Nephrogenic D.I results
from : from :
 hyposecretion of ADH  Kidneys don’t respond to
caused by : ADH .
brain tumor non-functional receptors
head trauma kidneys damaged
brain
surgery
 Most common symptoms :
 Polydipsia
 Polyuria
 Nocturia
 Treatment of neurogenic D.I :
 Hormone replacment , usually for life .
 Subcutaneous injection or nasal spray .