Vitamin D and the skin

The keratinocytes of the skin are unique in being not only the primary source of vitamin D for the body, but also possessing the enzymatic machinery to metabolize vitamin D to active metabolites [in particular, 1,25 dihydroxyvitamin D (1,25(OH)(2)D)] and the vitamin D receptor (VDR) that enables the keratinocytes to respond to the 1,25(OH)(2)D they produce. Numerous functions of the skin are regulated by vitamin D and/or its receptor: these include inhibition of proliferation, stimulation of differentiation including formation of the permeability barrier, promotion of innate immunity, regulation of the hair follicle cycle, and suppression of tumor formation. Regulation of these actions is exerted by a number of different coregulators including the coactivators DRIP and SRC, a less well known inhibitor, hairless, and beta-catenin. Different coregulators appear to be involved in different VDR-regulated functions. This review examines the various functions of vitamin D and its receptor, and to the extent known explores the mechanisms by which these functions are regulated.