Which second messenger pathway mediates the rapid (non-genomic) action of growth hormone (GH) on hepatocytes to produce IGF-1?

• A GH binding to GHR activates JAK2 (Janus kinase 2) which phosphorylates STAT5b; pSTAT5b dimerises and translocates to the nucleus to induce IGF-1 gene transcription ✓
• B GH activates Gs-adenylyl cyclase-cAMP-PKA, which phosphorylates CREB to induce IGF-1
• C GH activates phospholipase C-IP3 pathway releasing intracellular Ca2+ to activate calcineurin-NFAT signalling for IGF-1
• D GH binds a nuclear receptor and directly transactivates the IGF-1 promoter without cytoplasmic signalling

Explanation

Growth hormone receptor (GHR) is a cytokine receptor lacking intrinsic kinase activity. GH binding causes receptor dimerisation and activation of constitutively associated JAK2 (Janus kinase 2) by transphosphorylation. Activated JAK2 phosphorylates STAT5b (Signal Transducer and Activator of Transcription 5b) on tyrosine residues. Two pSTAT5b monomers dimerise and translocate to the nucleus, binding GAS elements in the IGF-1 promoter to drive IGF-1 transcription. Loss-of-function mutations in JAK2, GHR, or STAT5b cause GH insensitivity (Laron dwarfism) with elevated GH but low IGF-1.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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