Vitamin D, Calcium, and Epidermal Differentiation*

Abstract

THE SKIN is the sole source of cholecalciferol or vitamin D3 (D3), the precursor for a family of vitamin D metabolites whose best understood role is the regulation of bone mineral homeostasis (see Fig. 1). In the skin D3 is produced by a two-step mechanism from 7-dehydrocholesterol (7-DHC) (1). The first step, the breaking of the B ring after UV irradiation, results in the formation of pre-D3; the second step, the thermal conversion of pre-D3 to D3, provides for a sustained release of D3 to the body where it undergoes subsequent metabolism first in the liver to 25-hydroxyvitamin D3 (25OHD3) and then in a variety of tissues to additional metabolites, the most potent of which is 1,25- dihydroxyvitamin D3 [1,25(OH)2D3]. The plant sterol ergosterol undergoes a similar photoactivation to ergocalciferol or vitamin D2 (D2). D2 differs from D3 in that it contains a double bond between C22–23 and a methyl group at C24 of the side chain. In humans the metabolism of D2 and the potency of its metabolites are comparable to that of D3, allowing D2 to be widely used in pharmacological preparations in which a vitamin D supplement is desired. Although D3 and its metabolites are the natural form of this hormone family, this review will not, in general, use the distinguishing subscript because of the comparability between D3 and D2.