Vitamin D: A fountain of youth in gene regulation

The hormonal precursor and parent compound, vitamin D₃, either can be obtained in the diet or formed from 7-dehydrocholesterol in skin (epidermis) via a nonenzymatic, UV light-dependent reaction (Figure 1.1). Vitamin D₃ is then transported to the liver, where it is hydroxylated at the C-25 position of the side chain to produce 25-hydroxyvitamin D₃ (25D), which is the major circulating form of vitamin D₃. The nal step in the production of the hormonal form occurs mainly, but not exclusively, in the kidney via a tightly regulated 1α-hydroxylation reaction (Figure 1.1). The cytochrome P450-containing (CYP) enzymes that catalyze 25-and 1a-hydroxylations are microsomal CYP2R1 (Cheng et al. 2003) and mitochondrial CYP27B1, respectively. As depicted in Figure 1.1, 1,25-dihydroxyvitamin D₃ (1,25D) circulates, bound to plasma vitamin D binding protein, to various target tissues to exert its endocrine actions, which are mediated by the vitamin D receptor (VDR). Many of the long-recognized functions of 1,25D involve the regulation of calcium and phosphate metabolism, raising the blood levels of these ions to facilitate bone mineralization, as well as activating bone resorption as part of the remodeling cycle (Haussler et al. 2010).