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

The signalling pathways involved in melanogenesis have been partially eluci dated. The role of melanotropin peptides, alpha -MSH and ACTH, in melanocyt e differentiation and in the regulation of melanogenesis is now widely reco gnized. Their melanogenic effects appear to be mediated through;the up-regu lation of the cAMP pathway by the melanocortin-1 receptor and the activatio n of adenylate cyclase. The molecular mechanisms involve the subsequent pho sphorylation and activation of PKA, followed by CREB which binds to the pro moter of the transcription factor Microphthalmia, and upregulates its trans cription. The elevated expression of Microphthalmia increases its binding t o the specific E-box and M-box present in the tyrosinase promoter, resultin g in an increased expression of this enzyme and the up-regulation of melani n synthesis. LEF-1 and beta -catenin also regulate the expression of Microp hthalmia and play a key-role in pigment cell differentiation. Other transcr iption factors such as Brn2, TBX2, PAX3, Sox10 are also involved in these p rocesses. 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-kin ase/p70S6 kinase pathway. In addition, cAMP activates a melanocyte-specific pathway leading to MAP kinase activation. These new advances lead to a bet ter understanding of the natural photoprotective mechanisms of the skin. In the future, they should help to the development of treatments for pigmenta ry disorders, and more efficient prevention strategies against sun-induced ::carcinogenesis of human skin.