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 placenta.Yet the hCS peptide has only 0.1% of the growth-inducing potency of GH.

G H R H

• 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 calmodulin both stimulate GH release

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• reduces cAMP & free Ca+

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 target cells• ↓glu- uptake into cells• ↑lipolysis• ↑protein synthesis in

muscles• ↑ production of IGF

indirectly through IGF.• ↑ protein synthesis in

chodrocytes & ↑ linear growth• ↑ protein synthesis In

muscles & ↑ lean body mass.• ↑ 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 balancestimulate over all protein synthesisretention of phosphorus by inc-tubular reabsorptiondec- blood AA & NH3Inc- DNA and RNA synthesisinc- synthesis of collagenTransport & incorporation of A A in muscles

• EFFETC ON BONES & CARTILAGESDirect 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 early muscle cells.

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 HexokinaseIn 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 may impair

glucose uptake by both fat and muscle cells by a post receptor inhibition of insulin action.

Role of GH on minerals and ions

• ↑ intestinal absorption of Ca+

• Retains Na+, K+, Mg+,Po4

• PROLACTIN ACTION

Abnormalities of GrowthHormone 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 dwarfismGenetic defect in GH receptor., AR disorder.normal to high level of GH

and low IGF-1

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 hormones so that sexual functions are lost.

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 enlarged.