Peptides›GH secretagogue, Metabolic›Ghrelin (native)

Ghrelin (native)

/ Endogenous 28-residue peptide hormone (octanoylated at Ser3) — primary GHS-R1a ligand

TIER 3 · PreclinicalN = 0 · TESTING PENDINGMW 3370.90 g·mol⁻¹

ALIAS · Octanoyl-Ghrelin · Acyl-Ghrelin · Acylated ghrelin · Endogenous ghrelin

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceGSSFLSPEHQRVQQRKESKKPPAKLQPR (Ser3 modified by n-octanoyl group)

MW · 3370.90CLASS · Endogenous 28-residue peptide hormone (octanoylated at Ser3) — primary GHS-R1a ligandCATEGORY · GH secretagogue, Metabolic

Tier 3. Foundational endogenous peptide hormone with extensive preclinical literature; some Phase 1-2 human pharmacology studies of synthetic ghrelin infusions but no FDA-approved native ghrelin therapeutic. Synthetic ghrelin receptor agonists (anamorelin, capromorelin, ibutamoren) are the translational descendants.

§ B · Mechanism of action

Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a). It is produced primarily by P/D1 cells of the gastric fundus, with the n-octanoyl modification at Ser3 (catalysed by ghrelin O-acyltransferase, GOAT) being essential for GHS-R1a binding. Ghrelin signalling stimulates GH release at the pituitary, drives appetite via hypothalamic NPY/AgRP neurons, and modulates gastric motility, gastric acid secretion, and reward processing.

§ C · Human clinical evidence

Tier 3. Multiple Phase 1-2 human pharmacology studies of intravenous synthetic ghrelin infusion have demonstrated GH release, appetite stimulation, and gastric motility effects, but no Phase 3 trial of native ghrelin therapeutic. Synthetic agonists are the clinical translation path.

§ D · Primary literature

PubMed10604470Kojima M et al. — Ghrelin is a growth-hormone-releasing acylated peptide from stomach · Nature · in-vitroOriginal isolation and characterisation of ghrelin from rat stomach as the endogenous ligand of the orphan GHS-R; Ser3 octanoylation essential for receptor binding.Limitations: Discovery paper; no human dosing data.1999

PubMed11739476Wren AM et al. — Ghrelin enhances appetite and increases food intake in humans · The Journal of Clinical Endocrinology & Metabolism · human-phase-1Intravenous ghrelin infusion increased food intake by ~28% versus saline in healthy volunteers; first human demonstration of orexigenic effect.Limitations: Small n; acute infusion only; healthy normal-weight subjects.2001

§ F · Safety signal

In acute infusion studies, well tolerated; no chronic-administration safety database for native ghrelin. Class concerns about sustained GHS-R1a agonism (insulin resistance, glucose tolerance) apply.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The clinically relevant n-octanoylation requires GOAT enzyme; bulk synthesis of bioactive ghrelin is nontrivial. Vendor 'ghrelin' material may be the desacyl form (no octanoyl group), which has distinct biology and does not bind GHS-R1a meaningfully.