Ghrelin Receptor (GHSR-1a)

The ghrelin receptor (officially: Growth Hormone Secretagogue Receptor type 1a, GHSR-1a) is a G protein-coupled receptor expressed in the pituitary, hypothalamus, and other tissues. Its natural ligand is ghrelin — the hormone released from the stomach that drives hunger and also stimulates GH release. In the peptide world, the GHSR-1a is the target of a class of synthetic growth hormone secretagogues that work differently from GHRH analogs. Where sermorelin and CJC-1295 mimic the hypothalamic GHRH signal, compounds like ipamorelin and GHRP-6 mimic ghrelin and stimulate GH release through this separate receptor pathway. The distinction has clinical implications. GHRP-6, an older ghrelin receptor agonist, raises cortisol and prolactin alongside GH — which limits its utility. Ipamorelin was specifically developed to be selective for the GHSR-1a's GH-stimulating effect without triggering cortisol and prolactin elevation. That selectivity is the main argument for ipamorelin over GHRP-6 in the research literature. What neither class does: bypass the pituitary. Both GHRH analogs and ghrelin receptor agonists work by stimulating pituitary GH release. If the pituitary can't respond, neither class will work well.