The acyl-ghrelin–GHSR signalling axis

Scope and exact ligand identity

This page maps human receptor pharmacology, not treatment or the downstream growth-hormone axis. UniProt identifies ghrelin-28 as residues 24–51 of the 117-residue GHRL precursor. The mapped ligand is the 28-residue human sequence shown above with an O-octanoyl group on Ser3.

That modification is part of the ligand identity. A sequence string without the Ser3 acylation does not fully specify the canonical endogenous agonist represented by this edge.

The acylation gate

The discovery paper identified ghrelin as an acylated endogenous ligand for the growth hormone secretagogue receptor. UniProt records O-octanoyl, O-hexanoyl and O-decanoyl forms at the same precursor residue; this first atlas slice maps the originally defined octanoylated ghrelin-28 only.

Des-acyl ghrelin is not silently assigned the same receptor edge. Its biology requires a separate evidence review, and absence from this map is not a claim that it lacks every biological action.

Human GHS-R1a and primary transduction

GtoPdb identifies the human ghrelin receptor target with the GHSR gene and UniProt Q92847. Its primary curated transduction is Gq/11-family coupling → phospholipase C stimulation; the table renders the downstream IP3/Ca2+ step as the compact route label. GtoPdb also records secondary G-protein and G-protein-independent mechanisms, so “primary” is not “exclusive”.

The receptor has substantial constitutive activity and context-dependent signalling. This map therefore records an agonist edge without claiming that all observed signalling begins from a zero-activity baseline.

Separate engineered-ligand layer

GHRP-6 is a synthetic peptide research ligand. GtoPdb records it as a full agonist at the human ghrelin receptor, and the receptor-cloning paper places growth-hormone secretagogues at that target. The label “research ligand” is a pharmacological category here, not a medicine-approval claim.

Ibutamoren is structurally different: GtoPdb classifies it as a synthetic organic ligand and records full agonism at the human receptor. It is linked to the MK-677 monograph, while the dated status sources document clinical investigation under MK-0677 and FDA action against unapproved MK-677 products. These identity, target and status sources remain separate.

Evidence and naming boundaries

GHSR is the human gene; GHS-R1a is the functional receptor name used in this map. Ghrelin is the modified endogenous peptide, GHRP-6 is a synthetic hexapeptide research ligand, and ibutamoren is a non-peptide synthetic organic compound. Sharing a receptor does not make them chemically equivalent.

The edges do not rank potency, efficacy, bias or duration. They also do not extend receptor pharmacology into a claim about growth-hormone release, appetite, body composition or any other whole-organism result.

What this map cannot establish

A GHS-R1a agonist relation cannot by itself establish clinical benefit, a safe exposure, approval, product quality, suitability for an individual or a particular endocrine outcome. Those claims need their own human, regulatory and product-specific evidence. Full monographs are linked for that reason; their claims do not flow backwards into the receptor edge.