Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Available
Â
Anterior Pituitary Hormones.pdf
1. Dr. Koppala RVS Chaitanya
ANTERIOR PITUITARY HORMONES
Anterior pituitary (adenohypophysis), the master
endocrine gland, elaborates a number of important
regulatory hormones.
All of these are peptide in nature and act at
extracellular receptors located on their target cells.
Their secretion is controlled by the hypothalamus
through releasing and release-inhibitory hormones
that are transported via hypothalamohypophyseal
portal system, and is subjected to feedback
inhibition by the hormones of their target glands.
Each anterior pituitary hormone is produced by a
separate group of cells, which according to their
staining characteristic are either acidophilic or
basophilic.
The acidophils are either somatotropes GH; or
lactotropes: Prolactin. The basophils are
gonadotropes: FSH and LH; thyrotropes: TSH; and
corticotrope-lipotropes: ACTH.
The latter in addition to ACTH also produce two
melanocyte stimulating hormones (MSHs) and two
lipotropins, but these are probably not important in
man.
Fig.1: Action of growth hormone (GH) and
regulation of its secretion. GHRHâGrowth
hormone releasing hormone; IGF-1: Insulin
like growth factor-1; Stimulation (ââ
Inhibition (- - - -
2. Dr. Koppala RVS Chaitanya
HORMONES FEATURES PHYSIOLOGICAL PATHOLOGICAL PREPARATIONS
GROWTH
HORMONE
(GH)
īˇ Somatostatin also produced by D
cells of islets of Langerhans in the
pancreas
īˇ Receptors for GHRH and
Somatostatin are G protein
coupled receptors (GPCRs)
īˇ Somatostatin has also been shown
to inhibit Ca2+ channels and open
K+ channels.
īˇ Stimuli that cause GH release
areâfasting, hypoglycaemia,
exercise, stress and i.v. infusion of
arginine.
īˇ GH secretion is inhibited by rise in
plasma free fatty acid levels and
by high doses of glucocorticoids.
īˇ Dopaminergic agents cause a brief
increase in GH release in normal
subjects but
īˇ Paradoxically depress it in
acromegalies.
.
īˇ GH promotes growth of bones
and all other organs by
inducing hyperplasia.
īˇ Proportionate increase in the
size and mass of all parts
īˇ The growth of brain and eye is
independent of GH.
īˇ The positive nitrogen balance
īˇ The growth promoting,
nitrogen retaining and certain
metabolic actions of GH are
exerted indirectly through the
elaboration of peptides called
Somatomedins or Insulin-like
growth factors (mainly IGF-1,
also IGF-2)
īˇ Lipogenesis and glucose
uptake by muscles.
īˇ GH acts directly as well to
induce lipolysis in adipose
tissue,
īˇ Gluconeogenesis and
glycogenolysis in liver
īˇ Decreased glucose utilization
by muscles.
īˇ Gigantism in child
īˇ Acromegaly in adults.
Hypo secretion of GH
in children results in
pituitary dwarfism.
īˇ Adult GH deficiency
results in
īˇ Low muscle
īˇ Bone mass
īˇ Lethargy
īˇ Decreased work
capacity
hyperlipidaemia
īˇ Increased
cardiovascular risk.
īˇ Pituitary dwarfismâ
0.03â0.06 mg/kg daily
in the evening upto the
age of 20 years or
more.
īˇ Human GH produced
by recombinant DNA
technique (rhGH)
īˇ Somatropin (191AA)
is available for clinical
use.
īˇ GH Inhibitors:
Somatostatin
Octreotide
Lanreotide
Pegvisomant
PROLACTIN īˇ Prolactin is under predominant
īˇ Inhibitory control of hypothalamus
through PRIH
īˇ Which is dopamine that acts on
pituitary lactotrope D2 receptor.
īˇ Prolactin is the primary
stimulus which in conjunction
with oestrogens, progesterone
causes growth and
development of breast during
īˇ Galactorrhoea
īˇ Amenorrhoea
īˇ Infertility
īˇ Loss of libido and
depressed fertility.
Antagonist:
Bromocriptine:
īˇ Hyperprolactinemia
īˇ Acromegaly
īˇ Parkinsonism
3. Dr. Koppala RVS Chaitanya
īˇ Dopaminergic agonists (DA,
bromocriptine, cabergoline)
decrease plasma prolactin levels
īˇ Dopaminergic antagonists
(chlorpromazine, haloperidol,
metoclopramide) and DA deplete
(reserpine) cause
hyperprolactinemia.
īˇ Though TRH, prolactin releasing
peptide and VIP can stimulate
prolactin secretion, no specific
prolactin releasing factor has been
identified.
pregnancy.
īˇ It promotes proliferation of
ductal as well as acinar cells in
the breast and induces
synthesis of milk proteins and
lactose.
īˇ After parturition, prolactin
induces milk secretion
īˇ Prolactin suppresses
hypothalamo-pituitarygonadal
axis by inhibiting GnRH
release.
īˇ Continued high level of
prolactin during breastfeeding
is responsible for lactational
amenorrhoea, inhibition of
ovulation and infertility for
several months postpartum.
The causes of
hyperprolactinaemia are:
īˇ Disorders of
hypothalamus removing
the inhibitory control
over pituitary.
īˇ Antidopaminergic and
DA depleting drugs
īˇ Prolactin secreting
tumoursâthese may be
microprolactinomas or
macroprolactinomas.
īˇ Hypothyroidism with
high TRH levelsâalso
Increases prolactin
secretion.
īˇ Diabetes mellitus
(DM)
īˇ Hepatic coma
īˇ Suppresses lactation
īˇ Breast engorgement
Cabergoline
GONADOTR
OPINS (Gns)
īˇ A single releasing factor
(decapeptide designated GnRH) is
produced by the hypothalamus
which stimulates synthesis and
release of both FSH and LH from
pituitary.
īˇ It is, therefore, also referred to as
FSH/LH-RH or simply LHRH or
gonadorelin.
īˇ In females estradiol and
progesterone inhibit both FSH and
LH secretion mainly through
hypothalamus, but also by direct
action on pituitary.
īˇ FSH and LH act in concert to
promote gametogenesis and
secretion of gonadal
hormones.
īˇ FSH In the female it induces
follicular growth, development
of ovum and secretion of
estrogen.
īˇ In the male it supports
spermatogenesis and has a
trophic influence on
seminiferous tubules.
īˇ Ovarian and testicular atrophy
occurs in the absence of FSH.
īˇ Disturbances of Gn
secretion from pituitary
may be responsible for
delayed puberty or
precocious puberty.
īˇ Inadequate Gn secretion
results in amenorrhoea
and sterility in women;
īˇ Oligozoospermia,
īˇ Impotence
īˇ Infertility.
īˇ Excess production of
Gn in adult women
causes polycystic
Hormones analogues:
Menotropins
Urofollitropin
Menotropin
Follitropin Îą
Follitropin
Lutropin
Choriogonadotro
pin
Agonists:
Nafarelin,
Goserelin,
Triptorelin,
Leuprolide
4. Dr. Koppala RVS Chaitanya
īˇ However, the marked and
sustained preovulatory rise in
estrogen level paradoxically
stimulates LH and FSH secretion.
īˇ In addition there are other
regulatory substances, e.g.
Inhibinâa peptide from ovaries
and testes, selectively inhibits FSH
release, but not LH release.
īˇ Dopamine inhibits only LH
release. Testosterone is weaker
than estrogen in inhibiting Gn
secretion, but has effect on both
FSH and LH.
īˇ GnRH acts on gonadotropes
through a G-protein coupled
receptor which acts by increasing
intracellular Ca2+ through PIP2
hydrolysis.
īˇ The Gn secretion increases at
puberty and is higher in women
than in men. In men, the levels of
FSH and LH remain practically
constant (LH > FSH) while in
menstruating women they fluctuate
cyclically.
īˇ LH It induces preovulatory
swelling of the ripe Graafian
follicle and triggers ovulation
followed by luteinisation of
the ruptured follicle and
sustains corpus luteum till the
next menstrual cycle.
īˇ It is also probably responsible
for atresia of the remaining
follicles. Progesterone
secretion occurs only under the
influence of LH.
īˇ In the male LH stimulates
testosterone secretion by the
interstitial cells and is
designated interstitial cell
stimulating hormone (ICSH).
īˇ Distinct LH and FSH receptors
are expressed on the target
cells. Both are G protein
coupled receptors which on
activation increase cAMP
production.
ovaries.
īˇ In the testes FSH
receptor is expressed on
seminiferous (Sertoli)
cells while LH receptor
is expressed on
interstitial (Leydig)
cells.
īˇ In the ovaries FSH
receptors are present
only on granulosa cells,
while LH receptors are
widely distributed on
interstitial cells, theca
cells, preovulatory
granulosa cells and
luteal cells.
īˇ This in turn stimulates
gametogenesis and
conversion of
cholesterol to
pregnenoloneâthe first
step in progesterone,
testosterone and
estrogen synthesis.
Antagonists:
Ganirelix
Cetrorelix
Thyroid
Stimulating
Hormone
(TSH,
Thyrotropin):
īˇ Synthesis and release of TSH by
pituitary is controlled by
hypothalamus primarily through
TRH, while Somatostatin inhibits
TSH secretion.
īˇ Dopamine also reduces TSH
TSH stimulates thyroid to
synthesize and secrete thyroxine
(T4) and triiodothyronine (T3). Its
actions are:
īˇ Induces hyperplasia and
hypertrophy of thyroid
īˇ Only few cases of
hypoorhyperthyroidism
are due to inappropriate
TSH secretion.
īˇ In majority of cases of
myxoedema TSH levels
īˇ Thyrotropin has no
therapeutic use.
īˇ Thyroxine is the drug
of choice even when
hypothyroidism is
due to TSH
5. Dr. Koppala RVS Chaitanya
production induced by TRH.
īˇ The TRH receptor on pituitary
thyrotrope cells is a GPCR which
is linked to Gq protein and
activates PLCâIP3/DAGâcytosolic
Ca2+ pathway to enhance TSH
synthesis and release.
īˇ The negative feedback for
inhibiting TSH secretion is
provided by the thyroid hormones
which act primarily at the level of
the pituitary, but also in the
hypothalamus.
īˇ T3 has been shown to reduce TRH
receptors on the thyrotropes.
īˇ In human thyroid cells high
concentration of TSH also induces
PIP2 hydrolysis by the linking of
TSH receptor to Gq protein.
īˇ The resulting increase in cytosolic
Ca2+ and protein kinase C
activation may also mediate TSH
action, particularly generation of
H2O2 needed for oxidation of
iodide and iodination of tyrosil
residues.
follicles and increases blood
supply to the gland.
īˇ Promotes trapping of iodide
into thyroid by increasing
Na+: Iodide symporter (NIS).
īˇ Promotes organification of
trapped iodine and its
incorporation into T3 and T4
by increasing peroxidase
activity.
īˇ Enhances endocytotic uptake
of thyroid colloid by the
follicular cells and proteolysis
of thyroglobulin to release
more of T3 and T4. This
action starts within minutes of
TSH Administration.
īˇ The TSH receptor present on
thyroid cells is a GPCR which
utilizes the adenylyl cyclase-
cAMP transducer mechanism
(by coupling to Gs protein) to
produce its effects.
īˇ
are markedly elevated
because of deficient
feedback inhibition.
īˇ Gravesâ disease is due
to an immunoglobulin
of the IgG class which
attaches to the thyroid
cells and stimulates
them in the same way as
TSH.
īˇ Consequently, TSH
levels are low.
īˇ Contrary to earlier
belief, TSH is not
responsible for
exophthalmos seen in
Gravesâ disease because
TSH levels are low.
deficiency.
īˇ The diagnostic
application is to
differentiate
myxoedema due to
pituitary dysfunction
from primary thyroid
disease.
Adrenocorticot
ropic Hormone
(ACTH,
Corticotropin)
īˇ Hypothalamus regulates ACTH
release from pituitary through
corticotropin-releasing hormone
(CRH).
īˇ The CRH receptor on corticotropes
is also a GPCR which increases
īˇ Availability of cholesterol for
conversion to pregnenolone
which is the rate limiting step
in the production of gluco,
mineralo and weakly
androgenic steroids.
īˇ Excess production of
ACTH Cushingâs
syndrome.
īˇ Hypocorticism
īˇ ACTH is used
primarily for the
diagnosis of disorders
of pituitary adrenal
axis.
īˇ Injected i.v. 25 IU
6. Dr. Koppala RVS Chaitanya
ACTH synthesis as well as release
by raising cytosolic cAMP.
īˇ Secretion of ACTH has a circadian
rhythm.
īˇ Peak plasma levels occur in the
early morning, decrease during day
and are lowest at midnight.
īˇ A variety of stressful stimuli, e.g.
trauma, surgery, severe pain,
anxiety, fear, blood loss, exposure
to cold, etc.
īˇ Generate neural impulses which
converge on median eminence to
cause elaboration of CRH.
īˇ Arginine vasopressin (AVP)
enhances the action of CRH on
corticotropes and augments ACTH
release.
īˇ Induction of steroidogenic
īˇ Enzymes occur after a delay
resulting in 2nd phase ACTH
action.
īˇ The stores of adrenal steroids
are very limited and rate of
synthesis primarily governs
the rate of release.
īˇ ACTH also exerts trophic
influence on adrenal cortex
(again through cAMP): high
doses cause hypertrophy and
hyperplasia.
īˇ Lack of ACTH results in
adrenal atrophy.
īˇ However, zona glomerulosa is
little affected because
angiotensin II also exerts
trophic influence on this layer
and sustains aldosterone
secretion.
causes increase in
plasma cortisol if the
adrenals are
functional.
īˇ Direct assay of
plasma ACTH level
is now preferred.