Hypothalamus and Pituitary

gland
Dr.Annamalai.C
Physiology-Associate professor
Unisza kota kampus
Strictly for instructional use
 Learning objective
• Explain the functional structures of the endocrine
hypothalamus and the pituitary gland.
• Describe the functions of pituitary
hormones(growthhormone, vasopressin
oxytocin).
• Describe the regulation of the secretion of these
hormones.
• Discuss the clinical conditions associated with
their abnormal functions-gigantism, dwarfism
diabetes inspidus.
• 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. Between these is a small,
relatively avascular zone called the pars
intermedia, which is almost absent in the
human being but is much larger and much
more functional in some lower animals.
 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 Hypophyseal Portal System
 Hypothalamus
• 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 important pituitary hormones.
 Hypothalamic-Hypophysial Portal
Blood Vessels of the Anterior Pituitary
Gland
• The anterior pituitary is a highly vascular gland
with extensive capillary sinuses among the
glandular cells.
• Almost all the blood that enters these sinuses
passes first through another capillary bed in the
lower hypothalamus. The blood then flows
through small hypothalamic-hypophysial portal
blood vessels into the anterior pituitary sinuses.
The lowermost portion of the hypothalamus,
called the median eminence, which connects
inferiorly with the pituitary stalk.
 Endocrine Control: Three Levels
of Integration

• Hypothalamic stimulation–from CNS

• Pituitary stimulation–from hypothalamic trophic Hs
• Endocrine gland stimulation–from pituitary trophic Hs
Endocrine Control: Three Levels
of Integration

Hormones of the hypothalamic-anterior pituitary pathway

 Multiple Stimuli for Hormone
Release:
Nervous & Endocrine
• Stimuli
– Stretch
– Glucose
– Insulin levels
• Reflex
– Lower blood glucose
– Reduces stimulus
– Reduces insulin release
 Multiple Hormones Can Target a
Cell/Tissue
• Growth Hormone
• Somatomedins
• Thyroxin
– All have receptors
on many tissues
– Stimulate pathways
for growth

A complex endocrine pathway

 More Impacts on Target Cells
• Synergism: multiple stimuli more than additive
– Cortisol +5
– Glucagon +10
– Epinephrine +20 (added = +35)
– Synergistic effect + 140
• Antagonism: glucagons opposes insulin
• Permissiveness: need 2nd hormone to get full
expression
More Impacts on Target Cells

Synergism
• 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
• There is one cell type for each major hormone formed in the
anterior pituitary (( synthesize & secrete hormone )).

• five cell types can be differentiated :

• 1. Somatotropes—human growth hormone (hGH)

30- 40% of A.P cells .
• 2. Corticotropes—adrenocorticotropin (ACTH) – 20% of A.P cells .
• 3. Thyrotropes—thyroid-stimulating hormone (TSH)
3-5% of A.P cells
• 4. Gonadotropes—gonadotropic hormones, which include both luteinizing hormone
(LH) and folliclestimulatinghormone (FSH)
3-5% of A.P cells
• 5. Lactotropes—prolactin (PRL) – 3-5% 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 (GnRH) Stimulates secretion of FSH and LH by

gonadotropes

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

corticotropes

Growth hormone–releasing hormone Stimulates secretion of growth hormone

(GHRH) 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 and has a molecular weight of
22,005.

• 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.
D- Decreased Catabolism of Protein and Amino Acids.
• In the long run, this may be the most
important function of growth hormone.
 Ketogeni Effe t of Growth
Hormone
• GH causes release of fatty acids from adipose tissue and, therefore,
increasing the concentration of fatty acids in the body fluids.

• GH enhances the conversion of fatty acids to acetyl coenzyme A

(acetyl-CoA) and its subsequent utilization for energy.

• 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.

• Adequate insulin activity (amino acid transport) and

adequate availability of carbohydrates (energy) are
necessary for growth hormone to be effective.

• For these reaso s, growth hor o e’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.
III. specific effect of converting chondrocytes
into osteogenic cells, thus causing deposition
of new bone.
 Growth Hormone
• long bones grow in length at the epiphyseal
cartilages. This growth first causes deposition of
new cartilage, followed by its conversion into
new bone, thus lengthening the shaft and
pushing the epiphyses farther and farther apart.

• GH strongly stimulates osteoblasts. Therefore,

the bones can continue to become thicker
throughout life.
Growth Hormone Exerts Much of Its Effect Through Intermediate
“u stan es Called Somatomedins Also Called Insulin-Like
Growth Fa tors

• GH causes the liver and, to a much less

extent, other tissues to form several small
proteins called somatomedins that have
the potent effect of increasing all aspects
of bone growth – IGFs

• 4 somatomedins – somatomedin C (IGF-I)

 Short Duration of Action of Growth
Hormone but Prolonged Action of
Somatomedin C
• Growth hormone attaches weakly to the plasma
proteins in the blood.Therefore,it is released
from the blood into the tissues rapidly,
• having a half-time in the blood of less than 20
minutes.
• By contrast, somatomedin C attaches strongly to
a carrier protein in the blood ,
• As a result, somatomedin C is released only
slowly from the blood to the tissues, with a half-
time of about 20 hours.
 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 mobilization by growth,
adrenocorticotropic and thyroid hormones
• 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.
• 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
• 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
 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:
• Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg- GlyNH2
• Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2
• 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.
Antidiuretic hormone/ 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.
 Oxytocin
• 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 begins

By blood to Less than a minute
Breast Myoepithelial cells ( to flow
alveoli of the mammary
glands )
 Diabetes insipidus

• Defects in antidiuretic hormone receptors or

inability to secret ADH .
• Neurogenic D.I • Nephrogenic D.I results
results from : from :
 hyposecretion of  Kid eys do ’t respo d to
ADH 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 .
Major hormones secreted:
Secretory
Hormone Other names Symbol(s) Structure Staining Target Effect
cells
Secretion of
Adrenocorticot
Corticotropin ACTH Polypeptide Corticotrophs Basophil Adrenal gland glucocorticoid
ropic hormone
s
Inhibit
Opioid
Beta-endorphin Polypeptide Corticotrophs Basophil perception of
receptor
pain
Thyroid- Secretion of
stimulating Thyrotropin TSH Glycoprotein Thyrotrophs Basophil Thyroid gland thyroid
hormone hormones
Follicle- Growth of
stimulating - FSH Glycoprotein Gonadotrophs Basophil Gonads reproductive
hormone system
Luteinizing Sex hormone
Lutropin LH, ICSH Glycoprotein Gonadotrophs Basophil Gonads
hormone production
Promotes
growth; lipid
Growth Liver, adipose
Somatotropin GH, STH Polypeptide Somatotrophs Acidophil and
hormone tissue
carbohydrate
metabolism

Secretion of
Lactotrophs Ovaries,
Lactogenic estrogens/prog
Prolactin PRL Polypeptide and Acidophil mammary
hormone esterone; milk
Mammotrophs glands
production
 Hormones secreted:
Hormones known classically as posterior pituitary hormones are synthesized by the
hypothalamus. They are then stored and secreted by the posterior pituitary into the
bloodstream.

Hormone Other names Symbol(s) Target Effect Source

Uterine supraoptic and
Uterus, mammary
Oxytocin - OT contractions; paraventricular
glands
lactation nuclei

Stimulates water
Arginine
retention; raises
Vasopressin vasopressin, supraoptic and
Kidneys or blood pressure by
(antidiuretic argipressin, VP, AVP, ADH paraventricular
Arterioles contracting
hormone) antidiuretic nuclei
arterioles, induces
hormone
male aggression

Role in disease:
Insufficient secretion of vasopressin underlies diabetes insipidus, a condition in which the body
loses the capacity to concentrate urine. Affected individuals excrete as much as 20 liters of dilute
urine per day. Oversecretion of vasopressin causes the syndrome of inappropriate antidiuretic
hormone (SIADH).
 References

• Textbook of Medical physiology-AC

Guyton
• Review of medical physiology-WF
Ganong