Hexarelin

Hexarelin is a synthetic hexapeptide growth hormone-releasing peptide (GHRP) structurally related to GHRP-6 but incorporating D-2-methyltryptophan at position 2, which markedly increases both GHSR-1a affinity and resistance to enzymatic degradation. It is one of the most potent GHRPs identified, producing robust GH secretory responses in vivo with a good safety profile. In addition to its activity at the pituitary GHSR-1a (ghrelin receptor), hexarelin uniquely binds to the cardiac scavenger receptor CD36 (also known as the fatty acid translocase, FAT) — a receptor expressed on cardiomyocytes, endothelium, and macrophages — through a mechanism independent of GH secretion, conferring direct cardioprotective effects. Hexarelin's cardiac effects through CD36 include activation of PI3K/Akt/eNOS signaling leading to nitric oxide production and vasodilation, protection of cardiomyocytes from ischemia-reperfusion injury through anti-apoptotic mechanisms (Bcl-2 upregulation, cytochrome c retention), reduction of post-infarct ventricular remodeling, and anti-atherosclerotic effects through modulation of macrophage cholesterol efflux (CD36-mediated). These GH-independent cardiac effects make hexarelin a dual-mechanism peptide of particular interest in cardiovascular research — the CD36-binding activity provides a framework for developing non-GH-stimulating peptide derivatives that target cardiac CD36 for myocardial protection without the metabolic effects of GH excess. Hexarelin is used in research on growth hormone secretagogue pharmacology, cardioprotection mechanisms (ischemia-reperfusion, heart failure, cardiomyopathy), steroidogenesis (adrenal and gonadal GHSR-1a expression), and obesity-related metabolic research (GHSR-1a effects on energy homeostasis). The peptide is also used as a reference compound for evaluating GHSR-1a/CD36 dual-receptor ligand SAR, and in studies examining the independent contributions of GH-axis stimulation versus CD36-mediated signaling to hexarelin's observed pharmacological effects. Its high potency makes hexarelin a useful tool for characterizing GHSR-1a signal transduction pathways and for in vitro/in vivo GH stimulation challenge tests.