Tanning in the Dark?

Abstract

Fair-skinned people who experience difficulty tanning often have functional disruptions of MC1R (melanocortin 1 receptor), the receptor for melanocyte-stimulating hormone (MSH), and also have increased susceptibility to skin cancer. D’Orazio et al . used a line of red/blonde-haired, pheomelanin-producing mice with an inactivating mutation of the MSH receptor ( Mc1r e/e ) to explore the link between exposure to ultraviolet light (UV), MSH signaling, and tanning, as well as to UV-induced skin cancers. UV light elicited an increase in the mRNA encoding MSH in both primary human keratinocytes and the mouse PAM12 keratinocyte line; moreover, conditioned medium from UV-exposed PAM12 keratinocytes elicited a response in melanoma cells that was lost following absorption with an antibody to MSH. When exposed to UV, the ears of wild-type mice tanned, whereas those of Mc1r e/e mice did not. MC1R activates adenosine 3′,5′-monophosphate (cAMP) signaling. In a line of mice that expressed Mc1r e/e and that had (like humans but unlike wild-type mice) epidermal melanocytes in their truncal skin, topical treatment with the adenylate cyclase stimulator forskolin elicited eumelanin production and skin darkening. Furthermore, forskolin treatment protected against UV-induced "sunburn" and tumor production (mostly squamous cell carcinomas). Thus, the data suggest that small-molecule manipulation of MSH signaling could be used to influence skin pigmentation and might even be useful in preventing UV-induced skin damage and cancer. J. A. D'Orazio, T. Nobuhisa, R. Cui, M. Arya, M. Spry, K. Wakamatsu, V. Igras, T. Kunisada, S. R. Granter, E. K. Nishimura, S. Ito, D. E. Fisher, Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature 443 , 340-344 (2006). [PubMed]