Quick summary
Ghrelin is a 28-amino acid hormone and the only known circulating appetite stimulant. It activates GHSR-1a, triggering hunger and GH release. MK-677 (ibutamoren) was developed as an oral ghrelin mimetic.
Overview
Ghrelin is a 28-amino acid acylated peptide hormone primarily secreted by oxyntic cells in the gastric fundus. It is the only known circulating peptide that stimulates appetite (orexigenic). Ghrelin is also the endogenous ligand for the growth hormone secretagogue receptor (GHSR-1a), triggering pulsatile GH release. Its n-octanoyl modification at Ser-3 — added by the enzyme GOAT — is essential for GHSR binding and appetite stimulation. MK-677 (ibutamoren) was developed as a non-peptide oral ghrelin mimetic.
Mechanism of action
Ghrelin binds GHSR-1a, a constitutively active GPCR expressed in the hypothalamic arcuate nucleus, pituitary, and throughout the brain. Receptor activation stimulates GH release from pituitary somatotrophs via PLC-dependent signaling and activates hypothalamic NPY/AgRP neurons to increase food intake. Ghrelin also promotes reward-driven eating via dopamine release in the mesolimbic pathway (VTA, nucleus accumbens). Unacylated ghrelin (desacyl-ghrelin) circulates at higher levels and may have opposing metabolic effects through non-GHSR pathways.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| GH secretion research (animal) | intravenous | 1–10 nmol/kg | bolus, per protocol | |
| appetite/metabolic research | subcutaneous | 1–5 nmol/kg | daily, per protocol |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Ghrelin rises sharply before meals and falls postprandially, establishing it as a hunger signal. It is suppressed by caloric restriction in a manner that may undermine long-term weight loss. GH secretagogue research led to MK-677 (ibutamoren), an oral GHSR agonist that increases GH and IGF-1 over 24 hours in Phase 2 studies. Ghrelin receptor antagonists are being studied for obesity and addiction. GOAT (ghrelin O-acyltransferase) inhibitors are a therapeutic target to selectively suppress acyl-ghrelin without affecting desacyl-ghrelin.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Ghrelin for synergistic effects.
Legal status
Endogenous ghrelin peptide is available for research use only. Not FDA-approved for human administration. MK-677, a ghrelin receptor agonist, is a research compound not approved as a drug. GHRP-2 and GHRP-6 are related synthetic GHRPs also in research-only status.
Sourcing & access
Research compound
Ghrelin is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Ghrelin is a 28-amino acid peptide hormone primarily secreted by cells in the gastric fundus. It is the only known circulating peptide that stimulates appetite and is the endogenous ligand for the growth hormone secretagogue receptor (GHSR-1a). Its n-octanoyl modification at Ser-3 is essential for receptor binding.
Ghrelin binds GHSR-1a in the hypothalamic arcuate nucleus and pituitary, stimulating GH release and activating NPY/AgRP neurons to increase food intake. It also promotes reward-driven eating via dopamine release in the mesolimbic pathway. Unacylated ghrelin may have opposing metabolic effects through non-GHSR pathways.
Ghrelin is a research compound with side effects including increased appetite, transient GH elevation, water retention at high doses, and potential hyperglycemia via GH effects. Rapid inactivation by deacylation limits persistent effects in research settings.
MK-677 (ibutamoren) is an oral non-peptide ghrelin receptor agonist developed from ghrelin research. It increases GH and IGF-1 levels over 24 hours in Phase 2 studies. Unlike ghrelin peptide, MK-677 is orally bioavailable and has a much longer duration of action.
Ghrelin rises sharply before meals and is suppressed by caloric restriction, potentially undermining long-term weight loss. Ghrelin receptor antagonists and GOAT (ghrelin O-acyltransferase) inhibitors are being studied to selectively suppress appetite signaling for obesity treatment.
Research references
- Ghrelin is a growth-hormone-releasing acylated peptide from stomachPubMed
- From "Hunger Hormone" to "It's Complicated": Ghrelin Beyond Feeding ControlReview
- Molecular Mechanisms and Health Benefits of Ghrelin: A Narrative ReviewReview
- Ghrelin receptor signaling in health and disease: a biased viewPubMed
- Ghrelin-cell physiology and role in the gastrointestinal tractPubMed