GHRP-6
GHRP-6 is a synthetic hexapeptide that stimulates growth hormone release by activating the ghrelin receptor (GHS-R1a). It was one of the first growth hormone secretagogues and is not approved for any use.
Overview
GHRP-6 is a synthetic six-residue peptide developed in the late 1970s and 1980s by Cyril Bowers and colleagues, who were modifying enkephalin-like peptides and discovered sequences that released growth hormone from the pituitary. GHRP-6 became the prototype growth hormone releasing peptide. Its activity was later explained by the discovery of the growth hormone secretagogue receptor and, subsequently, of ghrelin, the endogenous hormone that activates the same receptor.
GHRP-6 has been studied in human pharmacology research and in animal models of cardiac, gastrointestinal and tissue injury. It is notable for stimulating appetite, consistent with its action at the ghrelin receptor, and for modest increases in cortisol and prolactin. It has not been developed into an approved drug, and its main use is as a research tool for ghrelin receptor and growth hormone axis biology.
Compare: GHRP-2 vs GHRP-6.
Structure
GHRP-6 is a hexapeptide with the sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2. It is fully synthetic, with no natural counterpart. The two D-amino acids (D-tryptophan and D-phenylalanine) are essential for activity and increase resistance to proteolysis, and the C-terminus is amidated. It contains two tryptophan residues, which makes it sensitive to oxidation and light. It is typically supplied as an acetate or trifluoroacetate salt.
Mechanism
GHRP-6 is an agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), the ghrelin receptor. In pituitary somatotrophs, receptor activation increases intracellular calcium and triggers growth hormone release. It acts synergistically with GHRH and partly by opposing somatostatin, and some of its effect is mediated through the hypothalamus.
Ghrelin receptors are also present in the hypothalamic appetite circuits, gut, heart and other tissues. Activation of hypothalamic receptors explains the appetite stimulation reported with GHRP-6. Studies have also described binding to CD36, a scavenger receptor in the heart, which has been proposed to contribute to cardioprotective effects seen in animal models, though this is not fully established.
Research
Growth hormone secretion physiology
GHRP-6 was used extensively in human physiology studies in the 1980s and 1990s to characterize growth hormone release, including its synergy with GHRH, its effects in different age groups and its use in testing pituitary function. These studies found robust growth hormone release along with modest rises in prolactin and cortisol. They were mechanistic investigations rather than trials of clinical benefit.
Cardiac injury in animal models
In rodent and swine models of myocardial ischemia and reperfusion, GHRP-6 administration was associated with reduced infarct size and preserved cardiac function in several studies. Proposed mechanisms include ghrelin receptor signaling and CD36 binding in cardiac tissue. These findings come from animal models, and there is no established human evidence for cardioprotective effects. Mechanistic work on cardiac CD36 binding is also largely preclinical.
Appetite and gastrointestinal research
Consistent with ghrelin receptor activation, GHRP-6 increases food intake in animal studies and has been reported to stimulate hunger in human pharmacology studies. Animal research has also examined its effects on gastric motility and gastrointestinal injury models. These observations make it a reference agonist for studying ghrelin signaling, but they do not establish clinical uses. Selective agonists such as ipamorelin have been used alongside it to separate these effects.
Regulatory status
GHRP-6 is not approved by the FDA or other major regulators for any use and is not an approved drug product. Its status for pharmacy compounding should be checked against current FDA guidance. Growth hormone secretagogues, including growth hormone releasing peptides such as GHRP-6, are prohibited at all times under section S2 of the WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A COA should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report purity by reverse-phase HPLC. The two tryptophan residues are the main stability concern: oxidized species (+16 and +32 Da, and kynurenine-type products) should be monitored. Because activity depends on the D-configured residues, stereochemical purity matters, and diastereomer impurities may co-elute on generic gradients. Confirm the C-terminal amide. Counter-ion (acetate or TFA) and net peptide content should be stated.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized GHRP-6 sealed at -20 °C, protected from light and moisture. The two tryptophan residues make it more sensitive to photo-oxidation than many short peptides, so amber vials or foil wrapping are advisable. Reconstituted laboratory solutions should be refrigerated, protected from light, used promptly and aliquoted to avoid repeated freeze-thaw cycles.
Download the GHRP-6 data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention GHRP-6 in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
What is the difference between GHRP-6 and ipamorelin?
Both are synthetic ghrelin receptor agonists that release growth hormone. GHRP-6 is the earlier prototype hexapeptide and is associated with appetite stimulation and modest cortisol and prolactin increases. Ipamorelin is a pentapeptide developed later that, in animal studies, released growth hormone without the adrenal effects reported for GHRP-6.
Is GHRP-6 FDA approved?
No. GHRP-6 is not approved by the FDA for any use. It has been studied in human pharmacology research and in animal models, but it has not completed the clinical development required for approval. Its status in pharmacy compounding should be checked against current FDA guidance. Other ghrelin receptor agonists share a similar investigational status.
Why is GHRP-6 associated with hunger?
GHRP-6 activates the ghrelin receptor, the same receptor targeted by ghrelin, a stomach-derived hormone that signals hunger to the hypothalamus. Animal studies show increased food intake after GHRP-6, and human pharmacology studies have reported increased hunger. This reflects the receptor's role in appetite regulation in addition to growth hormone release.
Related compounds
- Ipamorelin
Ipamorelin is a synthetic pentapeptide growth hormone secretagogue that acts as a selective agonist of the ghrelin receptor (GHS-R1a). It is investigational and not approved for any use.
- CJC-1295
CJC-1295 is a synthetic analogue of growth hormone releasing hormone (GHRH). The name properly refers to a version with a drug affinity complex (DAC) that binds albumin, but is also applied to modified GRF(1-29), which lacks DAC.
- Sermorelin
Sermorelin is a synthetic peptide consisting of the first 29 amino acids of human growth hormone releasing hormone (GHRH). It was previously FDA-approved as Geref but has been discontinued in the US.
- Tesamorelin
Tesamorelin is a stabilized synthetic analogue of human growth hormone releasing hormone. It is FDA-approved as Egrifta for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.
References
- PubMed: all indexed literature on GHRP-6
- ClinicalTrials.gov: registered studies mentioning GHRP-6
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