CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds

Abstract Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D 3 (20OHD) as a major product of vitamin D 3 . We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46 pmol/cm 2 against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98 ± 0.8%, ( p p p This article is part of a Special Issue entitled ‘17th Vitamin D Workshop’.