25-Hydroxyvitamin D 3 1α-Hydroxylase and Vitamin D Synthesis

Abstract
Renal 25–hydroxyvitamin D3 1α-hydroxylase [1α(OH)ase] catalyzes metabolic activation of 25–hydroxyvitamin D3 into 1α,25–dihydroxyvitamin D3[1α,25(OH)2D3], an active form of vitamin D, and is inhibited by 1α,25(OH)2D3. 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 (P450VD1 α). Expression of 1α(OH)ase was suppressed by 1α,25(OH)2D3 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.