Growth Hormone Secretagogue

Also known as: GHS · GH secretagogue · ghrelin mimetic

A growth hormone secretagogue (GHS) is a compound that makes the pituitary release its own growth hormone, usually by activating the ghrelin receptor.

"Secretagogue" just means something that triggers secretion, so the term is used loosely. In peptide discussions it usually means agonists of the growth hormone secretagogue receptor (GHS-R). That receptor's natural ligand is ghrelin, a 28-amino-acid peptide from the stomach that releases growth hormone; an octanoyl fatty-acid group on its third amino acid (serine 3) is essential for that activity. The ghrelin pathway is separate from the hypothalamic GHRH pathway, which is the target of GHRH analogs such as sermorelin, tesamorelin and CJC-1295.

Ghrelin-receptor agonists include the peptides GHRP-2, GHRP-6 and ipamorelin, and the oral non-peptide MK-677 (ibutamoren), described in trials as an oral ghrelin mimetic. They differ in selectivity. In animal pharmacology, GHRP-6 and GHRP-2 raised ACTH and cortisol as well as growth hormone, while ipamorelin did not, even at doses more than 200 times the dose needed for half its maximal growth hormone effect.

Why it matters

The strongest human data in this class are for MK-677. In a two-year randomized, placebo-controlled trial in 65 healthy adults aged 60 to 81, a daily oral dose raised growth hormone and IGF-1 to young-adult levels. After one year fat-free mass had risen by 1.1 kg on MK-677 and fallen by 0.5 kg on placebo, but strength and physical function did not change. Fasting glucose rose by an average of 5 mg/dL, insulin sensitivity fell and cortisol rose; appetite increased for a few months, and mild leg swelling and muscle pain were reported.

Ipamorelin and the GHRPs have much thinner human evidence than that; the key ipamorelin paper is animal and cell work. Because these compounds act on the ghrelin receptor, expect effects tied to growth hormone and IGF-1 and to ghrelin's role in appetite, not just a clean growth hormone pulse.

How to tell which kind of GH peptide you are looking at

Identify the receptor: ghrelin receptor (GHRP-2, GHRP-6, ipamorelin, MK-677) or GHRH receptor (sermorelin, tesamorelin, CJC-1295).
Check the evidence tier: a randomized human trial, a small human study, or animal and cell data.
Look beyond growth hormone: cortisol and ACTH, appetite, fasting glucose and insulin sensitivity.
Separate a lab change (higher IGF-1, more lean mass) from a functional outcome (strength, ability).

Worked example

In the MK-677 trial the between-group difference in fat-free mass at one year was 1.1 kg - (-0.5 kg) = 1.6 kg, yet strength and function did not improve.

Common mistakes

Lumping ghrelin-receptor agonists and GHRH analogs together without noting that they use different receptors.
Assuming more growth hormone means more strength; MK-677 raised fat-free mass without improving strength or function.
Ignoring glucose: MK-677 raised fasting glucose and lowered insulin sensitivity in older adults.
Treating ipamorelin's lack of cortisol release in pigs as proven in people.
Assuming that because release is pulsatile and "natural," there are no metabolic side effects.

Sources

Preclinical studyGhrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 1999. PMID 10604470.
Preclinical studyIpamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol, 1998. PMID 9849822.
Clinical trialEffects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med, 2008. PMID 18981485.

Page updated October 3, 2026. How we grade evidence: methodology.

Related Terms

GHRH Analog

A GHRH analog is a modified growth hormone-releasing hormone that activates the GHRH receptor on the pituitary to release the body's own growth hormone.

Stack

A stack is two or more compounds used during the same period, usually chosen because they are thought to act through different mechanisms on the same goal.

Receptor Agonist

A receptor agonist is a molecule that binds a receptor and switches it on, producing a response the way the body's own signaling molecule does.

Longevity Peptide

'Longevity peptide' is an informal label for peptides promoted to slow aging, such as Epitalon, MOTS-c and SS-31; evidence is mostly from cells and animals.

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