Hexarelin Research: GH Release, Desensitization and the CD36 Receptor
What the human and animal studies report about the most potent of the older GHRPs, including how the response fades with repeated exposure and why the heart appears in its literature.
Hexarelin is a synthetic hexapeptide growth-hormone-releasing peptide that acts at the ghrelin receptor, GHSR-1a. A PubMed search for hexarelin on 29 October 2026 returned 314 records, and the University of Turin endocrinology group around Ezio Ghigo appears as an author on 84 of them. This article summarises three themes in that literature: how it releases growth hormone, how the response changes with repeated exposure, and why a receptor in the heart features in its history.
Growth hormone release in humans
In a study from Turin, six normal young men received hexarelin by subcutaneous injection two or three times a day and had hormone levels sampled every 20 minutes for 24 hours. Both schedules raised 24-hour GH equally, by amplifying the mass of each secretory pulse rather than their frequency. Daily IGF-I, prolactin, ACTH and cortisol were unchanged. When hexarelin was given again at the end of the 24 hours, the GH response was blunted, the ACTH and cortisol responses were abolished, and the prolactin rise was not changed.
Desensitization
Whether the effect fades with repeated use is the central practical question. Rahim and Shalet gave twice-daily subcutaneous hexarelin to 12 healthy elderly people for 16 weeks. The area under the GH curve fell from 19.1 at week 0 to 13.1 at week 1, 12.3 at week 4 and 10.5 at week 16 (micrograms per litre per hour), with the falls at weeks 4 and 16 significant. After four weeks without treatment, hexarelin was given again and the response returned to 19.4, no different from the starting value. The authors concluded that attenuation after long-term treatment is partial and reversible.
A cell-based study points the same way. Orkin and colleagues showed rapid desensitization of the human ghrelin receptor to hexarelin in transfected Chinese hamster ovary cells, measured as the calcium response. For anyone designing repeated-exposure work, this is the main reason not to assume a constant response over time.
The heart and the CD36 receptor
Hexarelin attracted attention for cardiac effects that appeared to be independent of growth hormone. In 2002 Bodart and colleagues labelled rat cardiac membranes with a photoactivatable derivative of hexarelin and identified an 84 kDa binding protein as CD36. Activating CD36 in perfused hearts raised coronary perfusion pressure in a dose-dependent way, and the effect was absent in hearts from CD36-null mice and from a rat strain genetically deficient in CD36. A 2014 review describes CD36 as a specific cardiac receptor for hexarelin that mediates its cardioprotective effects, and notes that hexarelin is chemically more stable and functionally more potent than ghrelin.
Human cardiac data are small and acute. In one study of patients with severe left ventricular dysfunction, intravenous hexarelin raised GH in 8 patients with dilated cardiomyopathy and 5 with ischaemic cardiomyopathy alike, but the left ventricular ejection fraction rose only in the ischaemic group.
Safety and the evidence base
A 2018 review of growth hormone secretagogues, with no conflicts declared, concluded that the available studies describe them as well tolerated, with some concern about higher blood glucose because insulin sensitivity falls. It also noted that few long-term, rigorously controlled studies exist and that long-term safety, including cancer incidence and mortality, still needs to be evaluated.
QSC supplies hexarelin in 2 mg and 5 mg vials strictly for laboratory research. It is not approved for human or veterinary use, and this article is not medical advice or a dosing recommendation. For how hexarelin compares with GHRP-2 and GHRP-6, see our GHRP family overview.
Sources
Maccario M et al. Impact of two or three daily subcutaneous injections of hexarelin on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans. European Journal of Endocrinology, 2002;146(3):310-318. doi:10.1530/eje.0.1460310. PMID 11888836.
Rahim A, Shalet SM. Does desensitization to hexarelin occur? Growth Hormone and IGF Research, 1998;8 Suppl B:141-143. doi:10.1016/s1096-6374(98)80039-7. PMID 10990150.
Orkin RD et al. Rapid desensitisation of the GH secretagogue (ghrelin) receptor to hexarelin in vitro. Journal of Endocrinological Investigation, 2003;26(8):743-747. doi:10.1007/BF03347357. PMID 14669829.
Bodart V et al. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circulation Research, 2002 (3 May). doi:10.1161/01.res.0000016164.02525.b4. PMID 11988484.
Mao Y, Tokudome T, Kishimoto I. The cardiovascular action of hexarelin. Journal of Geriatric Cardiology, 2014;11(3):253-258. doi:10.11909/j.issn.1671-5411.2014.03.007. PMID 25278975.
Imazio M et al. GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy. European Journal of Heart Failure, 2002;4(2):185-191. doi:10.1016/s1388-9842(01)00223-9. PMID 11959048.
Sigalos JT, Pastuszak AW. The safety and efficacy of growth hormone secretagogues. Sexual Medicine Reviews, 2018;6(1):45-53. doi:10.1016/j.sxmr.2017.02.004. PMID 28400207.
PubMed record counts: query hexarelin, and the same query AND Ghigo[Author], run 29 October 2026.
