Neprilysin, a novel target for ultraviolet B regulation of melanogenesis via melanocortins

Compelling evidence suggest a role for melanocortins in the regulation of m elanogenesis by ultraviolet radiation. Within the epidermis, melanocytes an d keratinocytes produce a-melanocyte-stimulating hormone and adrenocorticot ropic hormone. The persistence and the strength of the biologic signal deli vered by these peptides depend on their local concentration, which is contr olled by the rate of peptide production and by the rate of its degradation. In this study, we investigated the mechanism of melanocortin degradation b y melanocytes and the effect of ultraviolet on this process. We have focuse d our attention on a neutral endopeptidase, neprilysin, which has been impl icated in the ending of numerous peptidergic signals. We have shown that th is enzyme is expressed at the surface of human melanocytes, Interestingly, its activity and its expression are dramatically downregulated by ultraviol et B treatment. Moreover, in the presence of phosphoramidon, a stable inhib itor of neprilysin, we observed an increased efficiency of alpha-melanocyte -stimulating hormone and adrenocorticotropic hormone to stimulate both tyro sinase activity and microphthalmia expression. Taken together, these data i ndicate that neprilysin expressed by melanocytes has a physiologic role in the regulation of melanogenesis by proopiomelanocortin peptide. Further, it s downregulation by ultraviolet B irradiation shed light on a new and appea ling mechanism of ultraviolet B induced melanogenesis via the control of me lanocortins degradation.