Research on Hexarelin Peptide?
Stimulates Growth Hormone Release: Research has shown that Hexarelin effectively stimulates GH release by binding to the GHS-R1a receptor in the pituitary and hypothalamus. Studies show Hexarelin induces a rapid and significant GH increase, often surpassing the response to GH-releasing hormone (GHRH). In children, it enhances GH secretion, even in cases of growth delay when primed with testosterone (1).
Studies in aged rats showed that long-term use helped keep growth hormone (GH) levels stable and improved the hypothalamic somatostatin mRNA patterns that regulate GH. This suggests potential benefits for anabolic (muscle-building), regenerative (repair), and metabolic processes. Hexarelin’s potent GH-releasing activity highlights its clinical utility in addressing GH deficiencies and related conditions (2).
Impact on Metabolism, Lipids, and Insulin Sensitivity: Research on Hexarelin has demonstrated significant metabolic benefits in insulin-resistant conditions, as shown in MKR mice. A 12-day treatment improved glucose tolerance, insulin sensitivity, and reduced plasma and liver triglycerides.
It also enhanced body composition by increasing lean mass and reducing fat mass. These effects are linked to improved lipid metabolism via CD36 receptor activation and PPAR-γ gene expression in adipocytes. Hexarelin shows potential for addressing insulin resistance and dyslipidemia in metabolic disorders (animal models) (3).
Bone Strength and Mineral Density: Studies have shown that Hexarelin enhances bone health in middle-aged female rats by increasing bone mineral content (BMC) and bone area. In intact rats, chronic hexarelin treatment (50 μg/kg twice daily for 60 days) improved BMC (+6.5%) and bone area (+4.1%) at lumbar vertebrae. In ovariectomized rats, it increased BMC (+7.2%) and bone area (+5.3%) at femoral mid-diaphyses. These effects suggest hexarelin’s potential to support bone strength via GH/IGF axis stimulation, influenced by estrogen levels (4).
Neuroprotection / Tissue-Protection: Studies suggest Hexarelin shows promising tissue-protective and neuroprotective effects. In a neonatal hypoxia-ischemia rat model, it reduced brain damage by 39%, decreased caspase-3 activity (a cell-death marker), and activated Akt/GSK-3β signaling (5).
In a study on a lung injury and fibrosis mouse model, hexarelin reduced inflammatory cell infiltration, improved lung compliance, and decreased collagen deposition, mitigating fibrosis. These findings suggest hexarelin’s potential in protecting against injury, oxidative stress, and fibrosis in experimental models (6).
Cardioprotective Effects: Research has demonstrated that Hexarelin has significant cardioprotective effects through GH-dependent and independent mechanisms. It improves cardiac output, reduces post-ischemic ventricular dysfunction, and decreases cardiac fibrosis. In human studies, hexarelin acutely increased left ventricular ejection fraction (LVEF) without altering blood pressure or heart rate, suggesting a direct myocardial effect via GHS receptors (7).
Additionally, hexarelin protects cardiomyocytes from angiotensin II-induced apoptosis by reducing caspase-3 activity, increasing Bcl-2 expression, and inhibiting Bax expression (8). In vascular models, hexarelin mitigates inflammation, smooth muscle cell dysfunction, and elastin degradation, highlighting its potential in conditions like myocardial infarction, heart failure, and aortic aneurysms (9).
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References
(1) S Loche, P Cambiaso, D Carta, S Setzu, et al (1995) The growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, in short normal and obese children and in hypopituitary subjects – Journal of Clinical Endocrinology & Metabolism, 1995 Feb, Volume 80 (Issue 2), Pages 674-8.
(2) L Cattaneo, M Luoni, B Settembrini, E E Müller, et al (1997) Effect of long-term administration of Hexarelin on the somatotrophic axis in aged rats – Pharmacological Research, 1997 Jul, Volume 36 (Issue 1), Pages 49-54.
(3) R Mosa, L Huang, Y Wu, C Fung, et al (2017) Hexarelin, a Growth Hormone Secretagogue, Improves Lipid Metabolic Aberrations in Nonobese Insulin-Resistant Male MKR Mice – Endocrinology, Volume 158, Issue 10, 1 October 2017, Pages 3174–3187.
(4) V Sibilia, D Cocchi, I Villa, N Lattuada, et al (2002) Bone effects of hexarelin, a GH-releasing peptide, in female rats: influence of estrogen milieu – European Journal of Endocrinology, 2002 Jun, Volume 146 (Issue 6), Pages 855-62.
(5) K G Brywe, A-L Leverin, M Gustavsson, C Mallard, et al (2005) Growth hormone-releasing peptide hexarelin reduces neonatal brain injury and alters Akt/glycogen synthase kinase-3beta phosphorylation – Endocrinology, 2005 Nov, Volume 146 (Issue 11), Pages 4665-72.
(6) V Zambelli, L Rizzi, P Delvecchio, E Bresciani, et al (2021) Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury – Drug Target Insights, 2021 Nov 27, Volume 15, Pages 26–33.
(7) G Bisi, V Podio, M R Valetto, F Broglio, et al (1999) Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans – Journal of Endocrinological Investigation, 1999 Apr, Volume 22 (Issue 4), Pages 266-72.
(8) J-J Pang, R-K Xu, X-B Xu, J-M Cao, et al (2004) Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro – American Journal of Physiology. Heart & Circulatory Physiology, 2004 Mar, Volume 286 (Issue 3), Pages H1063-9.
(9) B Jiang, M Wang, X Li, P Ren, et al (2022) Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation – Microvascular Research, 2022 Mar, Volume 140, Page 104280.