Physiology of Pituitary gland and its connections with Hypothalamus.

 At the end of the session the learner should be able to

 With the help of a labelled diagram describe the functional anatomy of Pituitary Gland by
enumerating its parts
 Describe the histological structure of pituitary gland.
 With the help of a labelled diagram describe the development of Pituitary Gland
 With the help of a labelled diagram describe the connections of Hypothalamus and Pituitary
Gland.
 Explain the endocrine functions of hypothalamus.
 Enumerate the Anterior pituitary hormones.
Development of Pituitary Gland
The Pituitary gland is developed from roof of the primitive oral cavity Rathke’s pouch it grows
upwards and fuses with the down growth from the median eminence and tuber cinereum. So
the anterior pituitary is ectodermal and posterior pituitary is neuroectodermal in origin. After
the embryogenesis the connection from the Rathke’s is lost whereas the connection from
hypothalamus to posterior pituitary is maintained.

Adenohypophysis is connected to hypothalamus through blood vessels-

Hypothalamohypophyseal portal system. This system of vascular connection is formed by
blood vessels from both superior and inferior hypophyseal blood vessels. They form primary
and secondary plexus and these plexuses are inter connected by long portal hypophyseal
vessels. The secondary plexuses are connected through short portal vessels
 Posterior pituitary gets long axons from supraoptic and paraventricular nuclei of
hypothalamus-Hypothalamohypophyseal neural tract. The secretion from hypothalamus
(supraoptic and paraventricular nuclei) ADH and Oxytocin are transported through
axoplasmic transport and later secreted to the blood according to the stimuli. The secretions
mainly trophic hormones are transported from various hypothalamic nuclei to anterior
pituitary through hypothalamohypophyseal portal vessels.
Histology of Pituitary Gland
The cells of pituitary gland are divided into
 Chromophobes-Agranular cells chromophils derived from chromophobes
 Chromophils-Acidophils , Basophils and Folliculostellate cells , Acidophils are further divided
into
 Somatotrophs
 Lactotrophs
 Basophils are divided into
 Gonadotrphs
 Thyrotrophs
 Corticotrophs
 Folliculostellate cells they possess processes sending to secretory cells concerned with
secretion of IL-6
 Pars tuberalis contains undifferentiated cells
 Pars intermedia-It contains Beta cells

Physiology of Growth hormone

Specific learning objectives

At the end of the session the learner should be able to d

 Describe the chemistry of Growth hormone

 Explain the mechanism of action of Growth Hormone
 Discuss the actions of growth hormone
 Explain the regulation of Growth hormone
 Explain the applied physiology of Growth Hormone.
Chemistry of Growth hormone
Growth hormone is a polypeptide hormone having 191 amino acids and synthesized
preprohormone in the ribosomes then it is converted to prohormone in the endoplasmic
reticulum. After release of peptide it is getting modified as hormone in the Golgi apparatus and
stored in the secondary vesicles then released in to the blood stream according to the stimuli.
There are two types of Growth hormones 22KGH and 20GH.

Tertiary structure of Growth Hormone

Polypeptide chain of Growth Hormone

Mechanism of Action of Growth Hormone
Mechanism of action of Growth hormone is same as that of a pepetide hormone
the receptors are located on the membrane when the hormone binds on the receptor the
they get dimerised the receptor becomes a homodimer. The signal transduction takes 4
pathways mainly

1. JAK-STAT pathway-Jak-2 is a member of the family of cytoplasmic cytosine

kinases Though it is not an integral part of the receptor it is having a major
role in signal transduction. STAT ia a cytoplasmic transcription activator and
also function as a signal transducer.STAT which gets phosphorylated by the
JAK kinases and binds on the DNA and induces transcription.
2. SHC- Grb Pathway- The JAK kinase phosphorylates the Grb2 proteins which
lates activates MAP kinases and induces various gene transcription.
3. TK-IRS- Pathway Activation of Tyrosine kinases like Jak kinase
phosphorylates the Insulin related substrate and then activate various
transcription inducers which are intra cellular enzymes.

4. Phospholipase -C Pathway- The hormone receptor complex activates the

membrane bound enzymes phospholipase C which results in the formation
of DAG (Diacyl glycerol) which activates the protein kinases and initiates
transcription.
 Regulation of Growth Hormone. – As shown in the digram below the
growth hormone is being regulated through hypothalamohypophyseal liver
axis.The hypothalamic factors GHRH and GHIH(Soatostatin) act on the
somatotrophs of anterior pituitary and the regulate the secreton according
to the stimuli.The growth hormone is having a negative feedback on the
GHRH and positive feedback on GHIH.The IGF-1 secreted in response GH
from the hepatocytes induces a negative feedback on pituitary as well as
hypothalamus. Other factors that mediates various effects through
hypothalamus are Stress, Sleep, Exercise various neurotransmitters like
catecholamines.

Applied Physiology. Hyper secretion of GH

Acromegaly- This clinical condition is the result of excess GH activity after the
fusion of epiphysis of long bones.As shown in the diagram below the membraneous bones
grow excessively and the face is showing a peculiar appearance (Ape like) prominence of
supraorbital ridge Prognathism (Over growth of lower jaw) broad nose .
The excess growth of the peripheral body parts like hands and feet the frequent change of
hand gloves and shoe sizes may be valuable clinical pointers.

Visceromegaly and most of the patients show glucose intolerance and later may result in
pituitary diabetes.The tumour from the somatotrophs enlarge the pituitary and result in the
pressure effect on the optic chiasma which is situated on the roof of sella tursica the central
fibers get damaged and cause bitemporal hemianopia.

Management-The diagnosis can be confirmed by the demonstration of tumor in pituitary

with CT scan or MRI scan the high level of plasma GH also is a diagnostic indicator. Surgical
removal of the tumor is the most accepted way of treatment.
Gigantism- Excess activity of GH before the fusion of epiphysis of long bones result in this
clinical condition. The individual will be much taller than the normal counter part as shown
in the diagram. There will be visceromegaly the excess growth of long bones may cause
arthritis and difficulty in locomotion. They also suffer from hyperglycemia.
 Dwarfism- It can be a genetic or clinical condition when the adult height is less than
147 cm or 4ft. There are various causes of dwarfism, as shown in the diagrams below. In
hypopituitarism the dwarfism is proportionate and both upper segment and lower segment
are of same proportion the intelligence will be normal but the reproductive organ
development is grossly reduced. The face of an adult resembles that of a child it is due to
the lack of secondary sexual charecters

Cretinism-Congenital hypothyroidism mostly due to the hypothyroidism of the mother

during pregnancy wherein the cause is hypothyroidism the short stature is characterised by
other features as shown in the photo below.One can susupect hypothyroidisnm from the
time of birth onwards by assessing the clinical features like Unhealthy cry at the time of
birth, delay in the passage of meconium (first stool) prolongation of physiological jaundice
delay in the attainment of motor and mental mile stones(as thyroid hormone plays a vital
role in the development of brain in the intrauterine life), Pot belly, protrusion of tongue,
yellowish discoloration of body due to hypercarotenaemia, unhealthy hair and mental . The
BMR will low, other clinical signs and biochemical parameters of hypothyroidism will be
evident.

Hypogonadism(Turner syndrome)- It is a genetic condition female child born with

absence of X chromosome or partial X clinical features include short stature with poorly
developed primary and secondary sexual characteristics. delayed puberty, and
infertility. While there's no cure, treatments like growth hormone and estrogen therapy can
help manage symptoms and improve quality of life.

Laron Dwarfism- A genetic disorder inherited as autosomal recessive form It is characterised

by the insensitivity to growth hormone due to the mutation of growth hormone receptor
mutation.The lack of synthesis of IGF 1 is also seen in this condition.

Hypogonadism – In certain geographical areas like China and Eygypt the chronic liver
dysfunction due to schistosomiasis and other regions like Iran it is due to Zinc deficiency
patients are having hepatospenomegaly hypogonadism and dwarfism.

Kasper Hauser syndrome (Psycho social dwarfism)-Kasper Hauser was a 17-year-old

dwarfed male, with a blank mind and without language, he exhibited a spurt of growth and
intellectual and social development, becoming a highly peculiar and limited young man whose origin
remained enigmatic when he was assassinated on December 14,1833.Kaspar Hauser syndrome" to
designate a previously poorly understood and described constellation of symptoms and findings he
and others have noted in small children who had been sequestered in their homes and subjected by
their caretakers to extreme neglect and other abuses. It can be attributed to the emotional factors
acting on hypothalamic causes resulting in reduced secretion of GHRH.