Find GHRH Products Interaction Network for GHRH GHRH Details

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Synonyms:GHRF, GHRH, GRF, Grh, MGC119781

GHRH Signaling

Hypothalamic-pituitary-mediated somatic growth (hypothalamic-pituitary somatotrophic axis) requires regulation of the secretion of growth hormone (GH) by pituitary somatotrophs via G-protein coupled receptors (GPCR). The secretion of GH from pituitary somatotrophs is stimulated synergistically by GH-releasing hormone (GHRH, GHRF, GRF, Somatocrinin) and ghrelin through their specific G-protein coupled receptors, GHRH-R and growth hormone secretagogue (GHS-R) receptor, respectively. GH secretion is inhibited by somatostatin (SRIF) through its GPCR receptor (SSTR, various subtypes). GHRH-R is a member of the secreting family of G-protein coupled receptors which also includes intestinal peptide, secretin, calcitonin, and PTH.

Growth hormone releasing hormone (GHRH, GHRF, GRF, Somatocrinin) is a forty four amino acid peptide synthesized by the hypothalamus that induces the expression and release of growth hormone (GH) from the anterior pituitary through GHRH receptors (GHRHR). GHRH-R exists in at least two isoforms that result from alternative splicing of a precursor mRNA. The short GHRH-R isoform is preferentially coupled to the adenylate cyclase (AC)/cAMP/protein kinase A pathway. The ghrelin receptor, GHS-R, also exists as two isoforms. The long isoform, Type 1a GHS-R, is preferentially coupled to phospholipase C (PLC)/inositol phosphate/protein kinase C (PKC) pathway.

GHRH-R activation causes the elevation of cAMP via G-protein alpha(s) (Gαs) subunit stimulation of adenylyl cyclase. The elevation of cAMP leads to the activation of protein kinase A (PKA) which phosphorylates and activates the transcription factor cAMP responsive element binding protein (CREB). CREB binds to and activates the promoter for GHF-1 (Pit-1) gene expression. GHF-1 (Pit-1) is a pituitary-specific transcription factor involved in regulation of the GHRH receptor and GH genes in somatotroph cells. PKA is also linked to a calcium-independent pathway for the elevation of cGMP via phosphorylation and stabilization of nitric oxide (NO)-dependent soluble guanylyl cyclase dimers (alpha(1)beta(1)-sGC heterodimers. GHRH stimulates MAP-kinase (ERK)-dependent proliferation of pituitary somatotroph cells by a PKA-independent pathway that has been linked to G-protein betagamma (Gβγ) subunit activation of a phosphoinositol 3 kinase (PI3-K)/Ras/Raf pathway.