| [ Summary ] |
The principal hormonal regulator of bone mineralization is vitamin D, which must be activated by a metabolic pathway consisting of a 25-hydroxylase and a 1 α-hydroxylase to yield 1 alpha, 25-dihydroxyvitamin D3. After many years of effort, the cDNA and gene for vitamin D hydroxylase enzymes were cloned. The expression of 25-hydroxyvitamin D3-1 alpha-hydroxylase (CYP27 B1) mRNA was greatly increased in the kidney of vitamin D-deficient rats. In rats with the enhanced renal production of 1 alpha, 25-dihydroxyvitamin D3 (rats feda low Ca diet), CYP27 B1 mRNA was greatly increased in the renal proximal convoluted tubules. However, renal expression of CYP27 B1 mRNA did not changed by a single injection of parathyroid hormone into normal rat. A single injection of calcitonin dose-dependently increased the expression of CYP27 B1 mRNA in the kidney of normocalcemic rats. On the other hand, 1 alpha, 25-dihydroxyvitamin D3 greatly increased the expression of 25-hydroxyvitamin D3-24-hydoroxylase mRNA in the kidney of vitamin D-deficient and-replete rats. Furthermore, recombinat CYP 24 catalizes the all the reactions in the C-24/C-23 pathway of 1 alpha, 25-dihydroxyvitamin D3 metabolism. It is likely that this enzyme by itself converts 25-hydroxyvitamin D3 1 alpfa , 25-dihydroxyvitamin D3 one of its final excretion products. |