GHRH analogs, growth factors, and the GH/IGF-1 axis
Growth hormone secretagogues are compounds that stimulate GH release from anterior pituitary somatotrophs. They operate at multiple levels of the GH/IGF-1 axis.
Hypothalamic GHRH stimulates somatotroph GH release, which triggers hepatic IGF-1 production. IGF-1 feeds back to suppress both hypothalamic GHRH and pituitary GH release. Somatostatin provides additional inhibitory control.
GHRH-R is a class B GPCR on pituitary somatotrophs. Ligand binding activates Gαs → adenylyl cyclase → cAMP → PKA. This cascade opens voltage-gated calcium channels and promotes GH exocytosis.
Related Compounds
MGF is a splice variant of IGF-1 produced locally in muscle tissue in response to mechanical stress. Unlike systemic IGF-1, MGF acts through autocrine/paracrine signaling to activate satellite cells. PEG-MGF extends this activity through PEGylation.
IGF-1 LR3 is a modified IGF-1 with reduced IGFBP binding, resulting in increased bioavailability and prolonged receptor engagement. It directly activates PI3K/Akt and Ras/MAPK cascades.
Studies focus on pulsatile vs continuous GH release patterns, the role of IGFBP in tissue-specific IGF-1 signaling, and local vs systemic growth factor pathways.
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