BINDING OF MELANOTROPIC HORMONES TO THE MELANOCORTIN RECEPTOR MC1R ONHUMAN MELANOCYTES STIMULATES PROLIFERATION AND MELANOGENESIS

alpha-Melanocyte stimulating hormone (alpha-MSH) and ACTH increase the proliferation and melanogenesis of cultured human melanocytes. To fur ther analyze how melanotropins produce these biological effects, we in vestigated the regulation of the melanocortin receptor MC1R expression by cy-MSH and ACTH using Northern blot analysis and determined the re lative affinity of the receptor for the structurally similar peptides alpha-MSH, ACTH, beta-MSH, and gamma-MSH. We also determined the relat ive potencies of these hormones to stimulate cAMP formation, tyrosinas e activity, and melanocyte proliferation. The order of affinity and po tency of the noted melanotropins in these assays were alpha-MSH = ACTH > beta-MSH > gamma-MSH. Because the binding affinity of each of these melanotropins for the MC1R correlated with its ability to stimulate h uman melanocyte proliferation and melanogenesis, we conclude that thes e effects are mediated specifically by binding to and activation of th e MC1R. gamma-MSH stimulated cAMP formation without affecting prolifer ation or melanogenesis. However, we found that relative to alpha-MSH, the effect of gamma-MSH on cAMP formation was transient. Our results s uggest that alpha-MSH, ACTH, and possibly beta-MSH, but not gamma-MSH, are capable of a physiological role in regulating human pigmentation, and that melanocytes in human skin are a specific target for these ho rmones.