Growth hormone is secreted by the anterior pituitary gland and regulates postnatal growth, protein synthesis, and metabolism. Its secretion is controlled by the hypothalamus through growth hormone-releasing hormone and growth hormone-inhibiting hormone. Growth hormone binds to receptors on target tissues and activates the JAK-STAT pathway to promote growth, increase fat metabolism, and influence protein and carbohydrate metabolism. Abnormal growth hormone secretion can cause gigantism, acromegaly, or dwarfism. Somatostatin and octreotide inhibit growth hormone secretion and are used to treat acromegaly.

1. Cellular and molecular mechanism of action of
Growth hormone
Presented by:
Mohd. Ashhar Suhail Nomani
M.Pharm 2nd Semester
Department of Pharmacology
Jamia Hamdard, New Delhi 1

2. Presentation Outline
• Introduction
• Regulation of secretion
• Growth Hormone Receptors
• Actions of GH
• Pathological involvements
• GH Inhibitors
• References
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3. GROWTH HORMONE
• Growth hormone(GH) or Somatotropic hormone(STH) is secreted by
acidophil cell of anterior pituitary gland.
• It is a polypeptide with 191 amino acid residue.
• Maintains lean body mass and bone mass in adults.
• Important for postnatal growth and development to adult size.
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4. VARIATIONS IN PLASMA LEVEL OF GH
• Birth to early childhood=
hormone level increases
• Children have higher
secretion than adult
• Puberty= have peak level of
GH
• Senescences= reduction of
GH
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5. REGULATION
• Hypothalamic
control
• Negative feedback
• Other control
mechanisms
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6. HYPOTHALMIC
CONTROL
• Control by 2
hormones
• Growth hormone
releasing hormone
(GHRH)
• Growth hormone
inhibiting hormone
(GHIH)
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7. GROWTH HORMONE RELEASING
HORMONE(GHRH)
• Polypeptide with 44 amino acids.
• Produced by hypothalamic neurons, stimulates GH secretion by binding to
specific GPCR on somatotrophs in the anterior pituitary.
• The stimulated GHRH receptor couples to Gs to raise intra-cellular levels of
cAMP and Ca2+, thereby stimulating GH synthesis and secretion.
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8. FACTORS STIMULATING GHRH SECRETION
• Hypoglycemia- through glucoreceptors in ventromedial nucleus of
hypothalamus(NE)
• Emotions, exercise & physical stress- pain, surgery, trauma & inflammation.
• Slow wave phase of sleep(5HT)
• Certain amino acids- arginine after protein meal
• Growth hormone releasing peptide(GHRP) – Ghrelin from oxyntic glands of
stomach.
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9. GROWTH HORMONE INHIBITING
HORMONE(GHIH)
• Somatostatin
• Polypeptide with 14 amino acids
• Factors stimulating GHIH-
Hyperglycemia
High FFA conc.
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10. NEGATIVE FEEDBACK
• By GH- by releasing somotostatin from
hypothalamus
• By GHRH- ultra short feedback loop
• By Somotomedins- Insulin like growth
factor (IGF) produced by action of growth
hormone on target tissue.
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11. OTHER CONTROL MECHANISMS
• Throxine , cortisol
• Insulin- represses GH gene expression
• Placental growth hormone & lactogen
• Obesity
• Nuerotransmitters – DA, NE, Ach, 5HT, GABA, histamine
• oestradiol
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12. GROWTH HORMONE RECEPTORS
• GH receptors of various sizes are present on the cell membrane in target
tissues, including the liver and adipose tissue.
• The GH receptor belongs to cytokine family of receptors and therefore
follows JAK-STAT pathway of cellular mechanism.
• It comprises a large extracellular portion, a transmembrane domain and a
large intracellular cytoplasmic portion.
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13. 13

14. Mechanism of Action
• Binding of one GH molecule to extracellular domain of a GH- receptor diamer
results in formation of ternary complex which undergoes a conformational change.
• That is followed by dimerization of receptors and activation of tyrosine kinase
enzyme known as Janus kinase 2 (Jak-2)
• This Jak-2 phosphorylate each other and tyrosine residues of the receptor.
• This leads to cascade of phosphorylation reactions result in activation of:
- proteins transcription(STAT)
- Mitogen activated protein(MAP) kinase
- Phosphoinositide-3-kinase (PI kinase)
• Overall results is linear growth and metabolism of carbohydrate, lipid, mineral &
protein as well as regulation of gene expression.
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15. ACTIONS OF GROWTH HORMONE
• Growth promoting actions
• Metabolic action
• Lactogenic actions
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16. GROWTH PROMOTING ACTIONS
• Promotes linear growth.
• Bone- stimulate osteoblastic activity converts cartilage into bone.
• Increases bone mass.
• Cartilage – stimulate proliferation of chondrocytes in epiphyseal
end plate of long bones.
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17. METABOLIC ACTION
PROTEIN METABOLISM (Positive Nitrogen Balance)
• Anabolic effect
• Promotes protein deposition in tissue.
• Increase amino acid uptake into cell
• Increase protein synthesis by ribosomes.
• Stimulates Transcription
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18. FAT METABOLISM
• Promotes Lipolysis in adipose
tissue.
• Increase fat utilization for energy.
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19. CARBOHYDRATE METABOLISM
• Antagonistic to insulin & produces
hyperglycemia.
• Increase Gluconeogenesis
• Decrease uptake & utilization of glucose by
by tissue for energy production
• Inhibit Glycolysis
• Increase Glycogen stores
• Use FFA for energy production.
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20. MINERAL METABOLISM
• Promotes bone mineralization in growing
children.
• Through IGF1 causes positive balance for
Ca, P and Mg.
• Promotes reabsorption of Ca, P & Mg.
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21. LACTOGENIC ACTIONS
• Enhances milk production
• Acts like Prolactin so called Prolactin like effect
of growth hormone.
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22. PATHOLOGICAL INVOLVEMENTS
• Excess production of GH is responsible
for gigantism in childhood and acromegaly
in adults.
• Hyposecretion of GH results in pituitary
dwarfism.
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23. GH INHIBITORS
• Somatostatin – 14 amino acid long peptide, inhibits GH, PRL, TSH, insulin,
glucagon, gastrin and HCl.
• GI actions causes steatorrhoea (the excretion of abnormal quantities of fat
with faeces), hypochlorhydria, dyspepsia and nausea.
• Use in acromegaly is limited because of duration of action is short(2-3 min)
• Octreotide- synthetic octapeptide surrogate of somatostatin
• 40 times more potent in suppressing GH secretion
• Longer acting( 90 min) therefore preferred over somatostatin for acromegaly.
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24. • Lanreotide – long acting octapeptide SST analogue that causes prolonged
suppression of GH secretion when administered subcutaneously.
• Its efficacy appears comparable to that of octreotide.
• Pegvisomant- GHR antagonist approved for treatment of acromegaly.
• It binds to GHR but does not activate JAK-STAT signalling or stimulate IGF1
secretion.
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25. REFERENCES
• Mark E. Molitch and Bernard P. Schimmer, ‘The Hypothalamic – Pituitary
Axis’; Goodman & Gilman’s ‘The Pharmacological Basis of Therapeutics’
13th Edition 2017, pp. 771-778
• Ritter M. et al., 2020 Rang and Dale’s Pharmacology. 9th Ed., Edinburgh:
Elsevier, pp 404-410
• F. Dehkhoda,Christine M.Lee, Andrew J. Brooks; 2018. ‘Growth Hormone
Receptor’. Sec. Molecular and Structural Endocrinology
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