Participation of the melanocortin-1 receptor in the UV control of pigmentation

The cloning of the melanocortin-1 receptor (MC1R) gene from human melanocyt es and the demonstration that these cells respond to the melanocortins alph a-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormon e (ACTH) with increased proliferation and melanogenesis have renewed the in terest in investigation the physiological role of these hormones in regulat ing human pigmentation. alpha-Melanocyte stimulating hormone and ACTH are b oth synthesized in the human epidermis, and their synthesis is upregulated by exposure to ultraviolet radiation (UVR). Activation of the MC1R by ligan d binding results in stimulation of cAMP formation, which is a principal me chanism for inducing melanogenesis. The increase in cAMP is required for th e pigmentary response of human melanocytes to UVR, and for allowing them to overcome the UVR-induced G1. arrest. Treatment of human melanocytes with a lpha-MSH increases eumelanin synthesis, an effect that is expected to enhan ce photoprotection of the skin. Population studies have revealed more than 20 allelic variants of the MC1R gene. Some of these variants are overexpres sed in individuals with skin type I or II, red hair, and poor tanning abili ty, Future studies will aim at further exploration of the role of these var iants in MC1R function, and in determining constitutive human pigmentation, the response to sun exposure, and possibly the susceptibility to skin canc er.