Alpha-MSH (Alpha-Melanocyte-Stimulating Hormone)

Hormonal / Appetite / Pigmentation

Also known as: Alpha-Melanocyte-Stimulating Hormone, alpha-MSH, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, POMC Fragment

MelanocortinsResearch phase: Endogenous hormone (well characterized)Regulatory: Endogenous peptide. Not used clinically. Synthetic analogs (afamelanotide, setmelanotide, melanotan-II) target specific MCR subtypes.

Mechanism

Alpha-MSH is the body's natural tanning and appetite-suppressing peptide. This 13-amino-acid fragment of POMC activates melanocortin receptors — MC1R in skin to produce melanin (pigmentation), and MC4R in the brain to suppress appetite. It is the endogenous peptide that inspired drugs like melanotan-II, PT-141, and setmelanotide.

Technical detail

Alpha-MSH (Ac-SYSMEHFRWGKPV-NH2) is a 13-amino-acid POMC cleavage product processed by prohormone convertases PC1/PC2 in the arcuate nucleus and pituitary. It activates MC1R (melanocytes: cAMP-PKA-MITF-tyrosinase cascade for eumelanin synthesis), MC3R (energy homeostasis), MC4R (hypothalamic appetite suppression via CREB signaling in PVN neurons), and MC5R (exocrine glands). It is antagonized by AgRP at MC3R/MC4R. Anti-inflammatory actions occur via MC1R on macrophages, suppressing NF-kB and reducing TNF-alpha/IL-6 production.

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