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GROWTH HORMONE

Growth
hormone(somatotropin)
• a water-soluble , polypeptide
• is the most abundant trophic
hormone in the anterior
pituitary
• a single chain of 191 amino acids
having two intramolecular
disulfide bonds.
• GHBP
• plasma half-life of 20 to 50
minutes.
• Inactivated by liver & kidneys
• The gene for GH is located on
chromosome 17.
• secreted by the somatotroph
(acidophilic )cells in the lateral
areas of the anterior pituitary
• structurally related to human
prolactin and hCS from the
GHRH
• Exist in 44 A.A
• Encoded on chromosome
20.
• Produced in cells of
arcuate nucleus.
• Full biological activity
resides in the first 29
amino acids of the N-
terminal portion of the
molecules.
• It interacts with sp-
receptors on
somatotrophs.
• The intracullular
signaling mech-
appeara to be multiple
but cAMP and calcium
G H Ri H
• Also called somatostatin
• Other sources are extra-
hypothalamic ,GIT,
placenta, ad- medulla
(these normally donot
influnce GH sec- by AP
b/c diluted by systemic
blood)
• It blocks the release of GH
induced by
secretogogues .e.g
• It contains 14 A A, cyclic
structure joined by an
intramolecular disulfide
bond b/w 2 cysteine.
• Two class of somatostatin
receptors exist.
• Binding activates G
proteins
Receptor of GH

• Receptors are
single
membrane-
bound protein
that belongs to
cytokine receptor
superfamily
• Hormone receptor
complex
activates a
tyrosine kinase
(jak-2)
Actions of GH

direct effect on
  indirectly through
target cells IGF.
• ↓glu- uptake into cells • ↑ protein synthesis in
chodrocytes & ↑ linear
• ↑lipolysis growth
• ↑protein synthesis in • ↑ protein synthesis In
muscles muscles & ↑ lean body
mass.
• ↑ production of IGF
• ↑ protein synthesis in
most organs & ↑ organ
size
Regulation of GH secretion
Factors regulating the GH
secretion
METABOLIC ROLE OF GROWTH
HORMONE
ON BODY PROTEINS
• PROTEIN SPARING EFFECT
 +ve nitrogen balance
 stimulate over all protein synthesis
 retention of phosphorus by inc-tubular
reabsorption
 dec- blood AA & NH3
 Inc- DNA and RNA synthesis
 inc- synthesis of collagen
 Transport & incorporation of A A in muscles
• EFFETC ON BONES & CARTILAGES
 Direct effect on chondrocytes stem cells→
IGF production
 act locally It ↑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
ON LIPID METABOLISM
• ACTIVATES ”harmone sensetive
lipase” lipolysis, -- more FFA
• ketogenesis

Growth Hormone Decreases
Carbohydrate Utilization
(1) decreased glucose uptake in tissues such as skeletal muscle and
fat, (2) increased glucose production by the liver,
(gluconeogenesis)and glycogenesis (3) increased insulin secretion.
Inhibits glucose uptake by sk- muscles by inhibiting Hexokinase
In liver it increases the activity of glucose-6-phosphtase
EFFECTS OF GROWTH HORMONE
ON ADIPOSE TISSUE
• ↑es the sensitivity of the adipocyte to
the lipolytic action of the
catecholamines
• ↓es its sensitivity to the lipogenic
action of insulin.
so release of FFA and glycerol ↑in the

blood
• metabolized by the liver.
• ↓ esterification of fatty acids, thereby
reducing triacylglycerol synthesis
within the fat cell.
• Recent evidence suggests that GH
Role of GH on minerals and
ions
• ↑ intestinal absorption of Ca+
• Retains Na+, K+, Mg+,Po4

• PROLACTIN ACTION


Abnormalities of Growth
Hormone Secretion
• Panhypopituitarism. may be congenital or
slowly at any time during life,
• most often resulting from a pituitary tumor that
destroys the pituitary gland.
• Dwarfism. A child who has reached the age of
10 years may have the bodily development of
a child aged 4 to 5 years, and the same
person at age 20 years may have the bodily
development of a child aged 7 to 10 years.
• A person with panhypopituitary dwarfism does
not pass through puberty and never secretes
sufficient quantities of gonadotropic
hormones to develop adult sexual functions.
• LARON-TYPE dwarfism
Genetic defect in GH receptor., AR

disorder.normal to high level of GH and low IGF-


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Panhypopituitarism in the
Adult
• tumorous conditions,
craniopharyngiomas or
chromophobe tumors, thrombosis
of the pituitary blood vessels.(This
abnormality occasionally occurs
when a new mother develops
circulatory shock after the birth of
her baby.)
• The general effects are (1)
hypothyroidism, (2) depressed
production of glucocorticoids by the
adrenal glands, and (3) suppressed
secretion of the gonadotropic
Gigantism.
• If the condition occurs before adolescence,
before the epiphyses of the long bones
have become fused with the shafts, height
increases so that the person becomes a
giant— up to 8 feet tall.
• The giant has hyperglycemia, islets of
Langerhans are prone to degenerate.
Consequently, in about 10 per cent of
giants, full-blown diabetes mellitus
eventually develops.
• usually causes death in early adulthood.
• However, once diagnosed, further effects
can often be blocked by microsurgical
removal of the tumor or by irradiation of
the pituitary gland.
Acromegaly.
• If an acidophilic tumor
occurs after
adolescence— after
the epiphyses of the
long bones have fused
with the shafts—
• the person cannot grow
taller, but the bones can
become thicker and the
soft tissues can continue
to grow..
• Enlargement is especially
marked in the bones of
the hands and feet and
in the membranous
bones, including the
cranium,
• , many soft tissue organs,
such as the tongue, the
liver, and especially the
kidneys, become greatly