Cyclic AMP is a key messenger in the regulation of skin pigmentation

The signalling pathways involved in melanogenesis have been partially elucidated. The role of melanotropin peptides, alpha -MSH and ACTH, in melanocyte differentiation and in the regulation of melanogenesis is now widely recognized. Their melanogenic effects appear to be mediated through;the up-regulation of the cAMP pathway by the melanocortin-1 receptor and the activation of adenylate cyclase. The molecular mechanisms involve the subsequent phosphorylation and activation of PKA, followed by CREB which binds to the promoter of the transcription factor Microphthalmia, and upregulates its transcription. The elevated expression of Microphthalmia increases its binding to the specific E-box and M-box present in the tyrosinase promoter, resulting in an increased expression of this enzyme and the up-regulation of melanin synthesis. LEF-1 and beta -catenin also regulate the expression of Microphthalmia and play a key-role in pigment cell differentiation. Other transcription factors such as Brn2, TBX2, PAX3, Sox10 are also involved in these processes. cAMP modulates several other signalling pathways involved in the regulation of melanogenesis. The cAMP-induced melanogenesis and dendricity are partially mediated by the inhibition of the pho sphatidylinositol-3-kinase/p70S6 kinase pathway. In addition, cAMP activates a melanocyte-specific pathway leading to MAP kinase activation. These new advances lead to a better understanding of the natural photoprotective mechanisms of the skin. In the future, they should help to the development of treatments for pigmentary disorders, and more efficient prevention strategies against sun-induced ::carcinogenesis of human skin.