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Hexarelin

Hexarelin belongs to a class of growth hormone secretagogues specifically known and referred to as Ghrelin mimetics or GHRPs. As opposed to GHRHs (growth hormone releasing hormones such as Sermorelin, Modified GRF 1-29, and CJC-1295), which are a separate class of growth hormone secretagogues, Ghrelin mimetics primarily increase growth hormone release in the somatotrophs within the pituitary. GHRHs, on the other hand, slighty increase somatotroph output while concurrently causing more somatrophs overall to release growth hormone.


Ghrelin mimetics have been demonstrated in clinical environments to release more growth hormone than GHRHs in comparison studies. [2] Ghrelin mimetics are less susceptible to environmental, hormonal, and physiological factors that inhibit GHRH-induced GH release, such as somatostatin, fatty acids circulating in plasma, and timing of the natural rhythmic growth hormone pulse in the human body. [1]


The most-studied Ghrelin mimetic peptides are GHRP-2, GHRP-6, hexarelin, and ipamorelin. Of these, ipamorelin is the least potent GH releasing compound but the compound that also has the least effect on cortisol and prolactin release. GHRP-6 is more potent with slightly more cortisol and prolactin release; GHRP-2 is more potent still; and hexarelin is the most potent of the four, with the most release of cortisol and prolactin as well. [3]


Each of the Ghrelin mimetics has unique properties largely unrelated, in most cases, to effecting the release of growth hormone from the pituitary. Hexarelin "reduces injury of cerebral cortex and hippocampus after brain hypoxia-ischemia in neonatal rats" according to one study; this effect may possibly be achieved with ghrelin, as well. [4] The ghrelin mimetics (GHRPs) are believed, as a whole, to potentially exert an antioxidant benefit on the testis by action involving the GHS-R type 1a present in Sertoli and Leydig cells; it may have antioxidant and anti-inflammatory effect through reduction of lipid peroxidation as well as increasing the activity of the body's three main antioxidant systems (superoxidate dismutase, glutathione peroxidase, and catalase), and may additionally protect spermatozoa from free radicals. [5]


Pang et al found, regarding hexarelin's potential cardioprotective effects, that:

GHS-R mRNA was abundantly expressed in cardiomyocytes and was unregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. [6]


In a separate study, Pang et al found data leading them to believe that hexarelin may have potential benefits in humans for treating atherosclerosis:

Hexarelin suppressed the formation of atherosclerotic plaques and neointima, partially reversed serum HDL-c/LDL-c ratio and increased the levels of serum NO and aortic mRNAs of eNOS, GHSR and CD36 in As rats. Hexarelin also decreased [(3)H]-TdR incorporation in cultured vascular smooth muscle cell (VSMC) and calcium sedimentation in aortic wall. Furthermore, foam cell formation induced by ox-LDL was decreased by hexarelin. In conclusion, hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in rats, possibly through up regulating HDL-c/LDL-c ratio, vascular NO production and downregulating the VSMC proliferation, aortic calcium sedimentation and foam cell formation. These novel anti-atherosclerotic actions of hexarelin suggest that the peptide might have a clinical potential in treating atherosclerosis. [7]


Bresciani et al concluded, due to findings that hexarelin induces hunger in rats even with chronic use, that "hexarelin is endowed with long-lasting orexigenic activity and might represent a potential therapeutic approach for pathological conditions characterized by a decline in food intake." [8]

Hexarelin resources:

[1]Penalva, A., Carballo, A., Pombo, M., Casanueva, F.F. and Dieguez, C. (1993) Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine or hypoglycemia on GHRP- 6-induced GH secretion in man. J. Clin. Endocrinol. Metab. 76, 168–171

[2]Bowers CY, Reynolds GA, Chang D, Hong A, Chang K, Momany F. A study on the regulation of GH release from the pituitary of rats, in vitro. Endocrinology 1981;108(3):1070–1079.

[3]Ghigo, E., Arvat, E., Muccioli, G. and Camanni, F. (1997) Growth hormone releasing peptides. Eur. J. Endocrinol. 136, 445–460

[4]Liu Y, Wang PS, Xie D, Liu K, Chen L. Ghrelin reduces injury of hippocampal neurons in a rat model of cerebral ischemia/reperfusion. Chin J Physiol. 2006 Oct 31;49(5):244-50.

[5]Kheradmand. Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin. Andrologia, Nov 2008, Volume 41, Issue 6, Pages 335-340

[6]Pang JJ, Xu RK, Xu XB, Cao JM, Ni C, Zhu WL, Asotra K, Chen MC, Chen C. Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro. Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1063-9. Epub 2003 Nov 13.

[7]Pang J, Xu Q, Xu X, Yin H, Xu R, Guo S, Hao W, Wang L, Chen C, Cao JM. Hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in the rat. Peptides. 2010 Apr;31(4):630-8. Epub 2009 Nov 30.

[8] Bresciani E, Pitsikas N, Tamiazzo L, Luoni M, Bulgarelli I, Cocchi D, Locatelli V, Torsello A. Feeding behavior during long-term hexarelin administration in young and old rats. J Endocrinol Invest. 2008 Jul;31(7):647-52.

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