Alpha-Melanocyte-stimulating hormone

α-Melanocyte-stimulating hormone (alpha-MSH; α-MSH), also known as alpha-melanotropin, alpha-melanocortin, or alpha-intermedin, is a naturally occurring endogenous peptide hormone of the melanocortin family, with a tridecapeptide structure and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It is the most important of the melanocyte-stimulating hormones (MSHs; also known as melanotropins) in stimulating melanogenesis, a process which in mammals (including humans) is responsible for pigmentation primarily of the hair and skin. It also plays a role in feeding behavior, energy homeostasis, and sexual activity.

α-MSH is a non-selective agonist of the melanocortin receptors MC1, MC3, MC4 and MC5, but not MC2 (which is exclusive for adrenocorticotropic hormone (ACTH)). Activation of the MC1 receptor is responsible for its effect on pigmentation, whereas its regulation of appetite, metabolism, and sexual behavior is mediated through both the MC3 and MC4 receptors.

It is generated as a proteolyic cleavage product from ACTH (1-13), which is in turn a cleavage product of proopiomelanocortin (POMC).

A couple of synthetic analogues of α-MSH have been investigated as medicinal drugs due to their photoprotective effects against ultraviolet (UV) radiation from the sun. They include afamelanotide (melanotan) and melanotan II, the former of which is in phase III clinical trials in the United States. Bremelanotide, another analogue of α-MSH, is currently under development not as a photoprotective agent, but instead for the treatment of sexual dysfunction. All of these drugs have significantly greater potencies than α-MSH, along with improved pharmacokinetics and distinctive selectivity profiles.