UV protection of the skin by topically-applied forskolin

Sun sensitivity and skin cancer risk are largely determined by skin complexion. Dark skin, which is UV-and cancer-resistant, is characterized by abundant deposition of melanin pigment in the epidermis. Melanin, which acts as a "sunblock" to physically interfere with penetration of damaging UV rays into the skin, is a pigment made by melanocytes that are positioned at the dermal-epidermal junction. Skin complexion is a polymorphic phenotype regulated by a number of genetic loci, however one of the most relevant to melanization of the skin and melanoma risk is the melanocortin 1 receptor (MC1R). Among human populations, loss-of-function of MC1R signaling due to inherited polymorphisms in the MC1R gene, are associated with a fair-skinned undermelanized, UV-sensitive and melanoma-prone phenotype. MC1R signaling, which is mediated by cAMP second messenger generation, can be pharmacologically stimulated by topical application of forskolin, a skin-permeable labdane diterpene which directly activates adenylyl cyclase. Here, we review skin physiology, focusing on the MC1R signaling pathway and pharmacologic induction of epidermal melanin and enhanced DNA repair by forskolin.