25-Hydroxyvitamin D3 1α-Hydroxylase and Vitamin D Synthesis

Renal 25–hydroxyvitamin D 3 1α-hydroxylase [1α(OH)ase] catalyzes metabolic activation of 25–hydroxyvitamin D 3 into 1α,25–dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ], an active form of vitamin D, and is inhibited by 1α,25(OH) 2 D 3 . 1α(OH)ase, which was cloned from the kidney of mice lacking the vitamin D receptor (VDR − / − mice), is a member of the P450 family of enzymes (P450 VD1 α ). Expression of 1α(OH)ase was suppressed by 1α,25(OH) 2 D 3 in VDR +/+ and VDR +/ − mice but not in VDR − / − mice. These results indicate that the negative feedback regulation of active vitamin D synthesis is mediated by 1α(OH)ase through liganded VDR.

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