25-HYDROXYVITAMIN-D-3 1-ALPHA-HYDROXYLASE AND VITAMIN-D SYNTHESIS

Renal 25-hydroxyvitamin D-3 1 alpha-hydroxylase [1 alpha(OH)ase] catal yzes metabolic activation of 25-hydroxyvitamin D-3 into 1 alpha,25-dih ydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3], an active form of vitamin D, and is inhibited by 1 alpha,25(OH)(2)D-3. 1 alpha(OH)ase, which was c loned from the kidney of mice lacking the vitamin D receptor (VDR-/- m ice), is a member of the P450 family of enzymes (P450(VD1 alpha)). Exp ression of 1 alpha(OH)ase was suppressed by 1 alpha,25(OH)(2)D-3 in VD R+/+ and VDR+/- mice but not in VDR-/- mice. These results indicate th at the negative feedback regulation of active vitamin D synthesis is m ediated by 1 alpha(OH)ase through liganded VDR.