Ghrelin

Ghrelin is a 28-amino acid peptide hormone produced primarily by X/A cells of the gastric fundus, discovered in 1999 by Kojima's Japanese team as the natural ligand of an orphan receptor named GHS-R (Growth Hormone Secretagogue Receptor). It carries a unique post-translational modification: acylation of its Serine 3 by an octanoic acid, a step catalyzed by the GOAT enzyme (Ghrelin O-Acyltransferase). Without this acylation, ghrelin loses its activity on GHS-R and becomes "non-acylated ghrelin", the majority form in blood but with distinct biological effects.

Physiologically, ghrelin is the hunger hormone: its plasma concentrations rise before meals and fall after food intake. It acts at the hypothalamic level (arcuate nucleus) to stimulate food intake, and at the pituitary level to amplify growth hormone secretion through GHS-R activation expressed on somatotropic cells. This dual function (orexigenic and somatotropic) makes it a major regulator of energy homeostasis, complementary to GLP-1 and leptin which exert anorexigenic actions.

Synthetic ghrelin analogues, called GH secretagogues (GHS), were developed to exploit the somatotropic branch of its biology without requiring the complex acylation of the native peptide. GHRP-6 (Growth Hormone Releasing Peptide-6), a first-generation hexapeptide, activates GHS-R effectively but also induces significant prolactin and cortisol secretion. Ipamorelin is a second-generation pentapeptide, designed for pure selectivity on GHS-R without collateral hypothalamic effects. MK-677 (ibutamorelin) is a small non-peptide orally active molecule, which maintains GHS-R activation for 24 hours.

In exploratory research, ghrelin analogues enable study of multiple biological questions: neuronal integration of energy signals in the hypothalamus, GPCR-β-arrestin signaling coupling mechanisms in pituitary cells, peripheral effects (heart, pancreas, bone) of ectopic GHS-R receptors, and indirect pharmacological regulation of the somatotropic axis. These molecules also serve as tools to validate new biomarkers of pulsatile GH secretion.

On lab-peptides-france.com, available GHS secretagogues include ipamorelin, GHRP-6, GHRP-2 and hexarelin, marketed for laboratory research only (RUO). Their use on humans outside authorized clinical trials is strictly prohibited. Available certificates of analysis are published on the relevant product pages.