Hexarelin Peptide

Hexarelin is a growth hormone-releasing peptide (GHRP) that has been suggested to exhibit activity similar to that of GHRP-6.(1) Also known as Examorelin, Hexarelin is a synthetic peptide composed of six amino acids.(2)

In terms of its proposed mechanism, Hexarelin is believed to mimic the action of ghrelin, a naturally occurring peptide consisting of 28 amino acids that is known to stimulate the release of growth hormone (GH) and influence appetite. Synthetic peptides such as Hexarelin, which appear to replicate aspects of ghrelin’s activity, were first developed more than 25 years ago.(3) Since their introduction, these compounds have been the subject of ongoing research aimed at better understanding their mechanisms and potential biological effects.

Overview

Hexarelin is hypothesised to act by mimicking ghrelin’s role in activating ghrelin receptors throughout the body, particularly within the hypothalamus and pituitary gland. These receptors—known as growth hormone secretagogue receptors (GHS-Rs), specifically GHSR-1a—are associated with the regulation of growth hormone (GH) release. Activation of these receptors may stimulate GH secretion, positioning Hexarelin as a potential growth hormone secretagogue. This mechanism represents an alternative pathway for GH regulation compared to the direct stimulation of the hypothalamus by endogenous growth hormone-releasing hormone (GHRH).

GHSR-1a receptors are distributed across the hypothalamus, pituitary gland, and various regions of the nervous system and peripheral tissues. As a result, Hexarelin is proposed to exert both direct and indirect effects on GH release—directly through pituitary receptor activation and indirectly through hypothalamic pathways.(4) Upon binding to these receptors, Hexarelin may induce conformational changes that activate intracellular signalling cascades, often mediated by G-proteins. This may involve activation of pathways such as protein kinase C (PKC), potentially amplifying signalling and promoting GH release from pituitary cells. However, repeated exposure to Hexarelin has also been associated with transient receptor desensitisation, which may persist for extended periods.(5)

In addition to its effects on growth hormone, Hexarelin has been suggested to influence the secretion of other pituitary hormones. These may include adrenocorticotropic hormone (ACTH) and prolactin, which may be elevated alongside GH in experimental settings.(6) Researchers have noted that this lack of selectivity may be a consideration when evaluating its broader endocrine effects.

Hexarelin’s interaction with GHS-Rs in other regions of the nervous system may also influence appetite regulation. It has been proposed that activation of these receptors could increase the production of hunger-related neuropeptides such as neuropeptide Y (NPY) and agouti-related peptide (AgRP), both of which play key roles in energy balance and appetite stimulation. At the same time, Hexarelin may reduce the release of melanocyte-stimulating hormone (α-MSH), an appetite-suppressing hormone, thereby shifting the balance toward increased food intake. Additionally, potential activation of GHSR-1a receptors within the mesolimbic reward system may influence food-related motivation and cravings, possibly through signalling pathways involving cyclic adenosine monophosphate (cAMP). Collectively, these mechanisms suggest that Hexarelin may play a role in modulating feeding behaviour and reward-driven eating patterns.(7)

Chemical Makeup

  • Molecular Formula: C47H58N12O6

  • Molecular Weight: 887.05 g/mol

  • Other Known Titles: examorelin

Research and Clinical Studies
Hexarelin Peptide and Growth Hormone Release

A study(8) was conducted across three groups of research models representing adolescent, mature, and elderly stages to assess the growth hormone (GH)-releasing potential of Hexarelin. In this investigation, all models were administered either Hexarelin, GHRH alone, or a combination of GHRH and arginine.

In adolescent models, the combination of GHRH and arginine was reported to produce the most notable increase in GH levels, while Hexarelin alone did not appear to significantly elevate GH in this group. In contrast, within both adolescent and mature models, Hexarelin appeared to induce higher GH levels compared to GHRH alone, and in some cases exceeded the effects observed with the GHRH and arginine combination.

In elderly models, Hexarelin was reported to increase GH levels to a greater extent than GHRH alone, although the increase remained lower than that achieved with the GHRH and arginine combination. Overall, these findings suggest that Hexarelin may have the potential to elevate GH levels, particularly in adolescent and mature models, while its effects in elderly and certain adolescent contexts appeared less pronounced or variable.

Hexarelin Peptide and Potential GHRH Synergism

The primary objective of this study(9) was to evaluate the potential effects of Hexarelin on the GH1 murine tumour cell line, which is considered to be relatively insensitive to growth hormone-releasing hormone (GHRH). The investigation also aimed to assess whether GHRH played any role in the observed actions of Hexarelin on these cells. Hexarelin was administered to both normal control murine pituitary cells and GH1 tumour cells. Researchers reported that GHRH increased growth hormone (GH) levels in normal pituitary cells but did not produce any noticeable effect in GH1 cells.

In contrast, when Hexarelin was administered, GH release appeared to occur independently of GHRH activity, suggesting that GHRPs and GHRHs may act via distinct biological pathways. These findings indicate that peptides such as Hexarelin may stimulate GH release even in cells that are unresponsive to GHRH. Notably, the researchers observed that “in this latter cell model, GHRH and Hexarelin were [posited] to have additive stimulatory effects on GH secretion,” suggesting that the two compounds may work through complementary mechanisms. This supports the hypothesis that combined activation of these separate pathways may result in a greater overall stimulation of GH synthesis compared to either agent alone.

Hexarelin Peptide and Cardiovascular Activity

Studies(10) have suggested that acute administration of Hexarelin may exert positive inotropic effects within the cardiovascular system. In experimental models, the peptide was associated with increases in left ventricular ejection fraction (LVEF), potentially without significant changes in blood pressure. In models with impaired coronary artery flow, Hexarelin appeared to enhance cardiac output and arterial pressure while maintaining a stable heart rate. Additionally, in ischaemic rat heart models, the peptide was reported to restore electrophysiological properties of cardiac cells and reduce apoptosis, suggesting a potential role in improving cardiac contractility and supporting cell survival.(11)

In a separate study,(12) Hexarelin was administered daily to murine models with experimentally induced myocardial infarction. The findings indicated that the peptide may increase stroke volume and overall cardiac output, while also reducing peripheral vascular resistance. These observations further support the potential influence of Hexarelin on cardiovascular function and haemodynamic performance.

Hexarelin Peptide and Composition

One study(13) investigated the potential relationship between body composition and the growth hormone-releasing effects of Hexarelin, with particular attention to sex-based differences. The findings suggested that the response to Hexarelin—specifically peak growth hormone release—was inversely correlated with fat mass. In other words, higher levels of body fat appeared to be associated with a reduced GH response following Hexarelin administration.

The study also reported that gender did not have a significant influence on growth hormone release in response to the peptide. These observations indicate that body composition, rather than sex, may play a more relevant role in modulating the GH-releasing effects of Hexarelin.

Hexarelin Peptide and Muscle Tissue

Preliminary experimental findings suggest that Hexarelin may exert muscle-sparing effects in research models subjected to catabolic conditions. Several studies have reported a reduction in both muscle mass loss and declines in muscle strength following exposure to catabolic agents, with these effects potentially associated with Hexarelin administration. For example, one study indicated that models exposed to catabolic conditions experienced approximately 12% muscle mass loss, whereas the inclusion of Hexarelin appeared to reduce this loss to around 7%.(14)

In a similar investigation,(15) the peptide was also associated with attenuation of strength loss typically observed under catabolic stress. These findings suggest that Hexarelin may play a role in preserving muscle tissue and functional capacity in conditions that promote muscle degradation, although further research is required to fully understand the underlying mechanisms.

Hexarelin peptide is available for research and laboratory purposes only. Please speak to our friendly research team to find out more and for sourcing options.

References:

  1. Giustina A, Bonfanti C, Licini M, Ragni G, Stefana B. Hexarelin, a novel GHRP-6 analog, stimulates growth hormone (GH) release in a GH-secreting rat cell line (GH1) insensitive to GH-releasing hormone. Regul Pept. 1997 May 14;70(1):49-54.   https://pubmed.ncbi.nlm.nih.gov/9250581/

  2. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 6918297, Examorelin. Retrieved August 19, 2021 from  https://pubchem.ncbi.nlm.nih.gov/compound/Examorelin

  3. Fabio Broglio et al, Ghrelin: Much more than a natural growth hormone secretagogue. Division of Endocrinology and Metabolism, Department of Internal Medicine; Division of Pathological Anatomy, Department of Biomedical Sciences and Oncology  https://www.ima.org.il/FilesUploadPublic/IMAJ/0/56/28152.pdf

  4. Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol. 1996 Oct;135(4):481-8.  https://pubmed.ncbi.nlm.nih.gov/8921832/

  5. Rahim, A., O'Neill, P. A., & Shalet, S. M. (1998). Growth hormone status during long-term hexarelin therapy. The Journal of clinical endocrinology and metabolism, 83(5), 1644–1649.   https://doi.org/10.1210/jcem.83.5.4812

  6. Massoud, A. F., Hindmarsh, P. C., & Brook, C. G. (1996). Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study. The Journal of clinical endocrinology and metabolism, 81(12), 4338–4341.  https://doi.org/10.1210/jcem.81.12.8954038

  7. Bresciani, E., Pitsikas, N., Tamiazzo, L., Luoni, M., Bulgarelli, I., Cocchi, D., Locatelli, V., & Torsello, A. (2008). Feeding behavior during long-term hexarelin administration in young and old rats. Journal of endocrinological investigation, 31(7), 647–652.  https://doi.org/10.1007/BF03345618

  8. Bellone J, Bartolotta E, Sgattoni C, Aimaretti G, Arvat E, Bellone S, Deghenghi R, Ghigo E. Hexarelin, a synthetic GH-releasing peptide, is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects. J Endocrinol Invest. 1998 Sep;21(8):494-500.  https://pubmed.ncbi.nlm.nih.gov/9801989/

  9. Giustina A, Bonfanti C, Licini M, Ragni G, Stefana B. Hexarelin, a novel GHRP-6 analog, stimulates growth hormone (GH) release in a GH-secreting rat cell line (GH1) insensitive to GH-releasing hormone. Regul Pept. 1997 May 14;70(1):49-54.  https://pubmed.ncbi.nlm.nih.gov/9250581/

  10. Mao, Yuanjie et al. “The cardiovascular action of hexarelin.” Journal of geriatric cardiology : JGC vol. 11,3 (2014): 253-8.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178518/

  11. Ma Y, Zhang L, Edwards JN, Launikonis BS, Chen C. Growth hormone secretagogues protect mouse cardiomyocytes from in vitro ischemia/reperfusion injury through regulation of intracellular calcium. PLoS One. 2012;7(4):e35265.   https://pubmed.ncbi.nlm.nih.gov/22493744/

  12. Tivesten A, Bollano E, Caidahl K, Kujacic V, Sun XY, Hedner T, Hjalmarson A, Bengtsson BA, Isgaard J. The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology. 2000 Jan;141(1):60-6.  https://pubmed.ncbi.nlm.nih.gov/10614623/

  13. Rahim A, O'Neill P, Shalet SM. The effect of body composition on hexarelin-induced growth hormone release in normal elderly subjects. Clin Endocrinol (Oxf). 1998 Nov;49(5):659-64.   https://pubmed.ncbi.nlm.nih.gov/10197083/

  14. Bresciani, E., Rizzi, L., Molteni, L., Ravelli, M., Liantonio, A., Ben Haj Salah, K., Fehrentz, J. A., Martinez, J., Omeljaniuk, R. J., Biagini, G., Locatelli, V., & Torsello, A. (2017). JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia.  Endocrine, 58(1), 106–114.  https://doi.org/10.1007/s12020-016-1184-2

  15. Conte, E., Camerino, G. M., Mele, A., De Bellis, M., Pierno, S., Rana, F., Fonzino, A., Caloiero, R., Rizzi, L., Bresciani, E., Ben Haj Salah, K., Fehrentz, J. A., Martinez, J., Giustino, A., Mariggiò, M. A., Coluccia, M., Tricarico, D., Lograno, M. D., De Luca, A., Torsello, A., … Liantonio, A. (2017). Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia. Journal of cachexia, sarcopenia and muscle, 8(3), 386–404.  https://doi.org/10.1002/jcsm.12185

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.

Hexarelin Peptide