melanocortin

Melanocortin is a family of peptide hormones derived from the precursor protein proopiomelanocortin (POMC). The melanocortin peptides include adrenocorticotropic hormone (ACTH) and the melanocyte-stimulating hormones α-MSH, β-MSH, and γ-MSH. In mammals these peptides are produced by proteolytic processing of POMC in pituitary corticotrophs and in various other tissues, where tissue-specific enzymes generate active fragments. The mature peptides exert their effects by binding to a distinct set of melanocortin receptors (MCRs), MC1R through MC5R, which are G protein-coupled receptors that signal mainly via cAMP.

Physiological roles of melanocortins are diverse. MC1R mediates pigmentation by stimulating eumelanin production in melanocytes; ACTH acts on MC2R in the adrenal cortex to stimulate glucocorticoid synthesis; MC3R and MC4R are highly expressed in the brain and regulate energy homeostasis, appetite, and body weight; MC5R has roles in exocrine function and other tissues. In addition to endocrine effects, α-MSH and other melanocortins exhibit anti-inflammatory properties in various models.

Genetic variation in melanocortin receptors, particularly MC1R, influences pigmentation phenotypes and skin cancer risk. Therapeutic research has explored MC4R agonists for obesity treatment and MC1R-targeted approaches for pigmentary disorders, while anti-inflammatory applications are under investigation.