α-MSH

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino-acid peptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂) derived from post-translational processing of the larger prohormone proopiomelanocortin (POMC) by prohormone convertase 2 in the intermediate pituitary, skin, and other peripheral tissues. It is the principal endogenous agonist of the melanocortin receptors MC1R (skin pigmentation), MC3R (energy homeostasis), MC4R (appetite, energy balance, sexual function), and MC5R (exocrine gland function), with negligible affinity for MC2R (ACTH receptor). The amino-terminal sequence is the cAMP-stimulating active core, while the C-terminal Lys-Pro-Val (KPV) tripeptide retains substantial anti-inflammatory activity that is mediated principally through intracellular NF-κB pathway interactions rather than membrane melanocortin receptors. α-MSH is studied for its dual role: as an agonist of MC1R for skin pigmentation and photoprotection (the basis of synthetic analogues afamelanotide, used clinically for erythropoietic protoporphyria; and bremelanotide/PT-141, used for hypoactive sexual desire disorder via MC4R), and as an anti-inflammatory mediator whose KPV fragment retains activity independent of melanocortin receptors. The latter property underlies KPV's research interest in inflammatory bowel disease and atopic dermatitis.