The pituitary gland is a small gland located at the base of the brain. It has an anterior and posterior lobe. The anterior lobe secretes growth hormone and other hormones that regulate many bodily functions. Growth hormone increases protein synthesis and breaks down fat. It also stimulates bone and cartilage growth. The posterior lobe stores and releases oxytocin and vasopressin (ADH) which are synthesized in the hypothalamus. Oxytocin stimulates uterine contractions and milk ejection while ADH regulates water balance.
3. Location
• The pituitary gland is also called as hypophysis
• It is derived from the greek word where hypo
means under and phyein means to grow
• It is a small gland of 1cm diameter and weight of
0.5 to 1 gm.
• Pituitary lies in sella turcica a bony cavity at the
base of the brain
• It is connected to the hypothalamus by the
pituitary hypophyseal stalk.
4.
5.
6. subdivisions
• The anterior pituitary is also known as
adenohypohysis
• The posterior pituitary is also known as
neurohypophysis
• Between these is a small avascular zone called as
pars intermedia
• Embrologically the anterior pituitary arises from
Rathke’s pouch and posterior pituitary from a
neural tissue outgrowth from hypothalamus
8. Cells of the anterior pituitary
Histological section shows three types of cells
1. Acidophis – they are cells that stain strongly
with acidic dyes
2. Basophis – they are cells that stain strongly
with basic dyes
3. Chromatophores- they are cells that do not
take up any stain
10. Secretoty cells of anterior pituitary
At least 5 different secretory cell types have been
identified in anterior pituitory by
immunocytochemistry and electron microscopy
• Somatotropes- growth hormone , somatotropin
• Corticotropes- adrenocorticotropin hormone
• Thyrotopes – thyroid stimulating hormone
• Gonadotropes – leuteinizing hormone and follicle
stimulating hormone
• Lactotropes (mammotropes) - prolactin
19. Growth hormone
• GHRH is a 39 amino acid peptide is synthesized in
arcuate nucleus
• GHRH release from arcuate nucleus is stimulated by
inputs from neurotransmitters, norepinephrine,
dopamine, serotonin and acetylcholine
• Growth hormone is secreted by somatotrophs which
comprise of half of cells i.e. 50 % of anterior pituitary
cells
• GH release is pulsative very low most of the day except
after meals, excersise and during slow wave sleep
20. Dopamine
• Dopamine is released from arcuate and
paraventricular nuclei that act on D2 receptors
to increase adenyl cyclase in lactotropes and
inhibit prolactin release
• It is unique because under normal conditions
the secretions is restrained and not elicited
• Prolactin is secreted by lactotropes which
constitute 15-30 % of the cells in normal
pituitary
21. LH and FSH
• LHRH is hypothalamically controlled by
hypothalamic factor that controls the release
of gonadotrophs
• LHRH is primarily released from arcuate
nucleus
• These hormones LH and FSH are secreted by
gonadotrophs which comprise of 10-20% of
adenohypophysis
22. TSH
• TRH is found in highest conc in medial division
of the paraventricular nuclei
• TSH is secreted by thyrotrops by about 5% of
the cells of pituitary
23. ACTH
• CRH primarily found in paraventricular nuclei
• The release of both ACTHand CRH are
inhibited by hormone cortisol
• ACTH is produced by corticotrophs that
comprise of 10% of the pituitary cells as part
of the larger pro-opiomelanocorticotropin
gene product from which melanocyte
stimulating hormone and β endorphins are
also derived
24. Proopiomelanocortin (POMC)
• Intermediate lobe and corticotropes of the anterior
pituitary both synthesize a large precursor protein that
is cleaved to form a family of hormones
• This molecule is also synthesized in the hypothalamus,
lungs gastrointestinal tract and placenta
• In corticotropes it is synthesized to ACTH, β lipoprotein
(γ-LPH), and a small amount of β endorphin
• POMC is hydolyzed to corticotropin like intermediate
lobe peptide (CLIP) in intermediate lobe cells
• The melanotropins α andβ –MSH are also formed
• The intermediate lobe in humans is rudimentary so
neither of the types of MSH is secreted in adults
25. Control of skin pigmentation
• Mammals don not have melanophores but melanocytes
containing melanin granules
• Melanocytes express melanotropin 1 receptors
• ACTH binds to melanotropin 1 receptors
• When there is change in ACTH levels there are changes in
pigmentation
• Abnormal palor is hallmark of hypopituitarism
• Other disorders of pigmentation occur from peripheral
mechanisms
• Like albinos have congenital inability to synthesize melanin,
piebaldism is characterized by patches of skin lacking
melanin, vitiligo olso has patchy loss of melanin but loss
occurs progressively after birth.
31. Sheehan syndrome
• During pregnancy the pituitary is enlarged
• The blood supply to the anterior lobe is
vulnerable because it depends in the pituitary
stalk
• Sometimes in an episode of shock due to post
partum hemorrhage the pituitary may
become infarct with development of post
partum necrosis
• This is known as sheehan syndrome
34. Cells of posterior pituitary
• The cells that secrete posterior pituitary
hormones are not located in posterior pituitary
• They are large magnocellular neurons
• These cells are located in supra optic and
paraventricular nuclei of hypothalamus
• The posterior pituitary is composed mainly of
glial like cells called pituicytes
• These cells simply act as supporting cells for
terminal nerve fibers and nerve ending
35. Posterior pituitary and its relation to
hypothalamus
• The hormones of posterior pituitary synthesized in hypothalamus is
transported in the axoplasm of neurons
• These nerve tracts pass to the neurohypophsis through hypophseal
stalk
• The nerve endings are bulbous knobs that contain many secretory
granules
• The hormone synthesized in cell bodies are transported with carrier
protiens neurophysins down to the nerve ending
• These nerve endings then secrete the two posterior hormones
oxytocin and ADH or arginine vasopressin (AVP)
• The transport takes several days to reach from the hypothalamic
nuclei to the posterior gland
36.
37. Secretion of post. Pituitary hormones
• The two hormones oxytocin and vasopressin are neural
hormones secreted into circulation by nerve cells
• The precursor molecules are synthesized in ribosomes
• They have their leader sequence removed in ER are then
packed into secretory granules in golgi apparatus and then
transported down the axons
• These secretory granules are called Herring bodies and are
easy to stain in tissue sections
• The secretions from secretory granules is released by
exocytosis in response to electical activity in the endings
• Both neurophysins and hormone are released together and
the separate immediately after release
38.
39.
40. Structure of hormones of post.
pituitary
• The posterior pituitary hormones are nanopeptides with
disulphide ring at one end
__S____________S___
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH
vasopressin
___S_____________S__
Cys-Try-Ile-Gln-Asn-Cys-Pro-Leu-Gly- NH
oxytocin
43. Physiological functions of ADH
• In absence of ADH the collecting tubules and
ducts become almost impermeable to water
which prevents significant reabsorbtion of
water causing extreme dilute urine
• In the presence of ADH the permeability of
the collecting ducts increases greatly and
allows most of the water to be reabsorbed
thereby conserving water resulting in
concentrated urine
44. Mechanism of action of ADH
Tubular epithelial cells with special vesicles that have
highly water permeable pores called aquaporins
ADH combines with membrane receptors and activates
formation of cAMP inside the cell
This causes phosphorylation of elements in special
vesicles
The vesicles then insert into the apical cell membrane
providing many areas of high water permeability
45. Regulation of ADH hormone
production
• Increased extracellular fluid osmolarity
stimulates antidiuretic hormone secretion
• Low blood volume and low blood pressure
stimulate ADH secretion – vasoconstricter
effect of ADH
46. Increased extracellular fluid osmolarity
• In the hypothalmus/organum vasculosum lies
modified neuron receptors called as osmoreceptors
• When extracellular fluid becomes too concentrated
fluid is pulled by osmosis out of osmoreceptor cells
decreasing its size and sending nerve signals resulting
in ADH release
• When the extracellular fluid becomes too dilute water
moves by osmosis into the cell this decreases the signal
for ADH release
• Regardless of the mechanism conc. Body fluids
stimulate supraoptic nuclei whereas dilute body fluids
inhibit them
47.
48. Low blood volume and low blood
pressure
• Minute concentration of ADH causes increased
water conservtion by kidneys
• High conc of ADH have a potent effectof
constricting the arterioles throughout the body
increasing arterial pressure
• So ADH gets the name vasopressin
• One of the stimuli for intense ADH release is
decreased blood volume
• The atria have strech receptors that are exited by
overfilling and inhibit ADH release whereas
underfilling will cause increased ADH release
52. Oxytocin hormone
• Oxytocin primarily acts on the breast and
uterus although it appears to be involved in
luteolysis also
• A G-protein coupled receptor has been found
in human myometrium and a similar receptor
is found in mammary tissue and ovary
• It triggers increase in intracellular calcium
levels
53. Contraction of smooth muscles
• The hormone oxytocin as the name suggest
powerfully stimulates contraction of the pregnant
uterus towards end of gestation
• The sensitivity of the uterine musculature to
oxytocin is enhanced by estrogen and inhibited
by progesterone
• After dialation of cervix, descent of fetus down
initiates impulses that are relayed to supraoptic
and paraventricular nuclei causing secretion of
hormone oxytocin to induce labour
54. Other effects of oxytocin
• Oxtocin may also act on nonpregnant uterus to
facitilate sperm transport
• The genital stimulation involved in coitus also
releases oxytocin
• Secretion of oxytocin is also increased by stressful
stimuli
• Oxytocin increases at the time of ejaculation in
males
• It also causes increased contraction of smooth
muscles of the vas deferens propelling sperm
towards the urethra
55. Other physiological effects of oxytocin
• Oxytocin is thought to modulate inflammation
by decreasing certain cytokines
• Due to similarity to vasopressin it can reduce
the excretion of urine slightly
• Oxytocin may play a role in autism and is
effective treatment for autisms repititive and
affiliative behaviour
• It is said to increase trust and reduce fear
• The are also said to be love hormones
56.
57. Milk ejection reflex
• The sucking stimulus on the nipple of the breast
causes signals to be transmitted through sensory
nerves to supra optic and paraventricular nuclei
which releases oxytocin from the posterior
pituitary
• The oxytocin is carried by the blood to the breast
where it causes contraction of myoepithelial cells
surrounding alveoli of mammary glands
• After the beginning of sucking milk begins to flow
this is called milk letdown or milk ejection
59. Pitocin
• It is a clear sterile solution of synthetic
oxytocin for intravenous or intramuscular
injection
• Pitocin if found in the pituitary extract from
mammals
• But it is prepared synthetically to avoid
possible contamination with vasopressin
• It is used to induce birth in pregnant womwn
who are post term or to speed up labor
61. Diabetes insipidus
Two types- central diabetes insipidus
- nephrogenic diabetes insipidus
• Central diabetes insipidus- they occur due to absence
of ADH hormone and result in large volume of dilute
urine. Treatment is a drug desmopressin that increases
water permeability and can be given as injection ,nasal
spray or orally
• Nephrogenic diabetes insipidus- there is normal level
of ADH but renal tubules cannot respond properly
resulting in large volume of dilute urine. The treatment
for this type is to correct the renal disorder
62. Syndrome of inappropriate antidiuresis
(SIAD)
• This is characterized by inappropriate secretion of
ADH
• It is a syndome of sodium and water imbalance
and manifested by hyotonic hyponatremia and
impaired urinary dilution
• The factors causing this may be endogenous,
exogenous or idiopathic causes
• Management of this condition requires
addressing all correctable causes i.e restricting
fluid intake and encouraging dietary intake of salt
and protein
63.
64. Growth hormone (GH)
• Growth hormone is also called somatotropic
hormone or somatotropin
• It 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 cells and
increased mitosis
65.
66.
67.
68.
69. Metabolic effects of growth hormone
(Direct effect)
1. Increased rate of protein synthesis in most cells
of the body
2. Increased mobilization of fatty acids from
adipose tissue, increased fatty acid in the blood
and increased use of fatty acid for energy
3. Decreased rate of glucose utilization throughout
the body
4. Thus it enhances body protein, uses up fat
stores and conserves carbohydrates
70. Protein deposition in tissues
• Enhancement of amino acid transport through
cell resulting in increased protein synthesis
• Enhancement of RNA translation causing
protein synthesis by ribosomes
• Increased nuclear transcription of DNA to
form RNA. This promotes more protein
synthesis
• Decreased catabolism of proteins and amino
acids
71. Fat utilization for energy
• Growth hormone causes release of fatty acids
from adipose tissue increasing conc. Of fatty
acids in fluids
• GH enhances conversion of fatty acids to acetyl
coenzyme and its subsequent utilization for
energy
• Excess of GH causes large amount of fat
mobilization and acetoacetic acids are formed by
liver resulting in ketosis this causes fatty liver
72. Decreased carbohydrate utilization
GH causes multiple effect to influence carbohydrate
metabolism
• Decreased glucose uptake in tissues like skeletal muscle
• Increased glucose production by liver
• Increased insulin secretion
• GH induces insulin resistance which stimulate the
uptake and utilization of glucose in skeletal muscles
and adipose tissue and inhibit gluconeogenesis
• GH effects are diabetogenic and excess secretion can
produce metabolic disturbance
73. Stimulation of cartilage and bone
growth (Indirect effect)
Most obvious effect of GH is to increase growth
of skeletal frame. This results from
• increased deposition of protein by
condrocytic and osteogenic cells that cause
bone growth
• Increased rate of production of these cells
• Specific effect of converting chondrocytes into
osteogenic cells thus causing deposition of
new bone
74. Mechanism of bone growth
1. In response to GH a long bone grows in length at
epiphyseal cartilage . This causes deposition of
new cartilage followed by conversion into new
bone thus elongting the shaft and pushing the
epiphysis farther apart. The epiphyseal cartilage
is progesssively used up so by adolecence no
epiphyseal cartilage remains for bone growth.
So there is no further growth of long bones.
There is fusion of shaft and epiphysis so no
futher lengthening of long bone can occur
75. Mechanism of bone growth
2.Osteoblast in bone periosteum and in some bone
cavities deposit new bone on surface of older
bone. Osteoclast in bone remove old bone.
When rate of deposition is greater than
resorbtion the thickness of the bone increases.
GH strongly stimulate osteoblast. Bones
continue to grow under influence of GH. This is
true for membranous bones like jaw bones that
grow after adolesence causing forward
protrusion of chin and lower teeth.
78. Insulin like growth factors
(Somatomedins)
• GH causes liver to form several small proteins called as
somatomedins that have potent effect of increasing all
aspects of bone growth
• These effects are similar to effects of insulin on growth
so they are called insulin like growth factors
• 4 somatomedins have been isolated and most
important is somatomedin C (Insulin like growth factor
-1 /IGF-1
• The pygmies of Africa have a congenital inability to
synthesize significant amounts of somatomedin C and
so account for small stature
79. Regulation of growth hormone
• Adolecents have the highest circulaing levels
of growth hormone followed by children and
then adults
• In old age it falls to about 25% of the
adolecent levels
• There has been considerable interest in
injecting GH hormone to counterbalance the
effects of aging.
80. Pulsative pattern of GH secretion
• There is also diurnal variation in growth
hormane superimposed by developmental
stages
• GH hormone characteristically increases
during first 2 hrs of deep sleep and large
pulsative burst of GH secretion occures
• It is found at relatively low levels during the
day unless specific triggers for its release is
present.
81. Factors that stimulate secretion
• Starvation especially severe protein deficiency
• Hypoglycemia or low conc. Of fatty acids in blood
• Exercise
• Excitement
• Trauma
• Grelin a hormone secreted by stomach before
meals involved in regulating food intake
82.
83.
84. Abnormalities of growth hormone
secretion
Panhypopituitarism-
• It is decreased secretion of all anterior pituitary
hormones
• In adults it may be due to tumor or due to
thrombosis of pituitary blood vessel
• It results in hypothyroidism, decreased
glucocorticoids and suppressed gonadotropic
hormones
• So the person will be lethargic, who is gaining
weight and who has lost all sexual functions
85. Dwarfism
• In most instances this results from panhypopituitarism
during childhood
• The physical parts of the body develop in appropriate
proportions to one another but rate of development is
greatly decreased
• This person never passes through puberty and does
not secrete gonadotropin hormones
• 1/3 of such dwarfs do mature sexually and ocassionally
reproduce
• Some dwarfs have normal or high GH but there is
hereditary inability to form somatomedin C for
promotion of growth.
86. Types of dwarfism
• Laron dwarfism- plama Gh conc. is normal or elevated but
growth receptors are unresponsive due to mutations
• African pygmy have normal plasma level of GH and growth
binding proteins however the somatomedins fail to
increase at puberty
• Short stature can also be seen in hypothyroidsm- cretinism
• Stunted growth is also seen in gonadal dysgenesis and
chromosomal abnormalities
• Psychosocial dwarfism or kaspar Hauser syndrome is seen
in children due to chronic abuse and neglect
• Achondroplasia- most common dwarfism charcterised by
short limbs and normal trunk. It is an autosomal dominant
condition caused by mutation in the gene.
87. Gigantism
• The acidophilic GH producing cells of anterior pituitary
become excessively active
• There is large production of GH hormone
• All body tissues grow rapidly including bones
• If condition occurs before adolecence it results in increase
of height –giant-upto 8 ft tall
• The giant ordinarily has hyperglycemia and slowly β cells of
islets of Langerhans degenerate due to hyperglycemia
• If untreated panhypopituitarism develops because the
gland itself gets destroyed slowly due to tumor
• Once diagnosed tumor can be microsurgically removed
• Death usually occurs in early adulthood
88. Acromegaly
• If the acidophilic tumor occurs after
adolescence that is after the long bones have
fused with the shaft the bone cannot grow
long but becomes thicker
• This condition is called acromegaly