GROWTH HORMONE“ACTION”

INTRODUCTIONGrowth Hormone is also called somatotropin hormone. It is synthesized by the acidophils of anterior lobe

and stored in very large amounts in the pituitary gland. Daily GH output(adults/children) is 0.2 to 1 mg/day, with biological half life 6-20 min.

Human GH is a single unbranched polypeptide chain containing 191 amino acids with molecular weight of 22,005

It varies considerably in structure from species to species.

Growth Hormone does not function through a target gland but exerts its effects directly on all tissues of the body .

MECHANISM OF HORMONAL ACTION 1.ACTION THROUGH MEMBRANE PERMEABILITY:

bind with the receptor that causes confirmational change in protein receptor that results opening or closing of channels.

2.ACTION THROUGH THE EFFECT OF GENE EXPRESSION these hormones are lipophilic they easily pass through the cell membrane.

3.ACTION THROUGH SECONDARY MESSENGER:It include AMP & GMP SYSTEM.4.ACTION THROUGH TYROSINE KINASE

ACTIVATION:It include -hormone receptor that possess intrinsic

tyrosine activity. -hormone receptor that NOT possess

intrinsic tyrosine activity.

ACTIONS OF GROWTH HORMONE 1. STIMULATION OF GROWTH OF BONE ,

CARTILAGE AND CONNECTIVE TISSUE The effects of growth hormone on skeletal growth

mediated by family of polypeptide called somatomedins.

GROWTH HORMONE increase the number of cells.

e.g. in muscles and bones . THYROID HORMONE AND INSULIN They are also necessary for normal osteogenesis

insulin increase cytoplasmic growth. Thyroid hormone required for full effect of GH

on DNA replication .

• GROWTH FACTORSa. Somatomedin A and B;b. Insulin like growth factor I and II ; c. Nerve growth factor (NGF);d. Ovarian growth factor (OGF);e. Epidermal growth factor (EGF);f. Fibroblast growth factor (FGF);g. Thymosin;h. Multiplication simulating activity(MSA); andi. Platelet derived growth factor(PDGF).j. Relaxin.

INSULIN LIKE GROWTH FACTOR I AND II

IGF-I(or somatomedin C)

IGF-II(or multiplication stimulating activity )

1. Secretion : Independent of GH before birth but is stimulated by GH after birth ;peak secretion at the time of puberty and decreases in old age.

2. Plasma level :10-700 ng/ml3. Receptor: Similar to insulin

receptor4. Major action:

i.Growth stimulating activity; ii.Control of skeletal and

cartilage growth.

1. Independent of GH. Its secretions are constant throughout postnatal growth.

2. 300-800 ng/ml3. Mannose-6-phosphate

receptor involved targeting proteins to intracellular organelles.

4. Growth during foetal development.

‘Receptors’ for somatomedins exist in chondrocytes,hepatocytes,adipocytes and muscle cells.

SOMATOMEDIN has insulin like effect on tissues,including lipolysis,increased glucose oxidation fat and increased glucose and amino acid transport by muscle.

Somatomedin activity rises peak 16-20 hours after injection of GH.

SOMATOMEDIN ACTIVITY REDUCES BY Glucocorticoids and protein deficiency.

Before Epiphysial Closure- GH through somatomedin , stimulate

proliferation of chondrocytes , appearance of osteoblast.

Stimulation of DNA & RNA synthesis and collagen formation.

Increase in the thickness of epiphysial end plate.

• After epiphysial closure- bone length can no longer increase by GH but

bone thickening can occur through Periosteal growth .

Seen in hypersecretion of GH (ACROMEGALY)

2.Effects on protein and Mineral metabolism • On protein metabolism : GH is protein

anabolic hormone. Mechanism of action:a. It effects ribosomal attachmentb. It increase transport of neural and basic

amino acid into cells from E.C.F. Therefore , plasma amino acid level decreases. This effect is unaffected by protein synthesis blocking drugs.

c. It increases excretion of amino acids i.e. 4-hydroxyproline,which comes from collagen. Thus , hydroxyproline excretion is increased in:

- diseases associated with increased collagen destruction, and

- when synthesis of soluble collagen is increased.

d. It stimulates erythropoesis.

• On mineral metabolism:

a. Increases Ca2+ absorbtion from GIT.b. Decreases Ca2+ ,K+ , Na+ and phosphorus

excretion from kidneys, because these minerals are diverted from kidneys to the growing tissues.

3. Effect on carbohydrate and fat metabolismOn carbohydrate- GH is DIABETOGENICa. Increasing hepatic glucose output ; and

b. Directly antagonizing the insulin effect on adipose tissue and skeletal muscle .

• On fat metabolism :a. GH has catabolic effect. i.e. it increases

mobilization of fat from adipose tissues , increase circulating ‘FFA’ Level. This provides ready source of energy for tissues during hypoglycemia,fasting and other stressful stimuli.

b.GH has ketogenic effect. i.e increases hepatic oxidation of fatty acid to keto bodies.

Increases ability of pancreas to respond to insulinogenic stimulation.

4. On kidneysFollowing removal of anterior pituitary,i. Kidney size decreasesii. GFR decreasesiii. Renal blood flow decreases andiv. Tubular secretion of PAH decreases 5.On Thymus: GH increases growth of thymus

(which is often enlarged in ACROMEGALY).6.Increases milk production : GH can increase

lactation in women.

Applied AspectGROWTH RETARDATIONCan occur when GH levelsAre increased and somatomedin levels are

depressede.g. in kwashiorkor

African pygmies: Their plasma IGF-I conc. Fails to increase in puberty.• Laron Dwarfism: there is Co genital abnormility of GH receptors therefore Plasma conc. of GH binding decreases and IGF-I not secreted in sufficient amount.

• Gigantism: due to over production of GH in adolesence i.e. before epiphysial closure.

• Acromegaly :It is associated with hypersecretion of prolactin . It causes growth of those areas where cartilage persist.

REFERENCESGUYTON AND HALLNOTESWIKIPEDIAADAM.COM