Inhibition of 25-Hydroxyvitamin D3Production by 1,25-Dihydroxyvitamin D3in Rats

The regulation of the hepatic vitamin D325-hydroxylase enzyme system by 1,25-dihydroxyvitamin D3was examined using male rats. Circulating 25-hydroxyvitamin D3levels decreased in response to increasing doses of 1,25-dihydroxyvitamin D3as determined by HPLC and serum protein binding assay. A maximum reduction in serum 25-hydroxyvitamin D3of 57.7% was achieved by the administration of 1,25-dihydroxyvitamin D3and higher doses produced no further reduction. Thein vitrorate of vitamin D 25-hydroxylation by liver homogenates from rats given 1,25-dihydroxyvitamin D3was also reduced by 60.4%. Whole rat extracts from animals given [3H]vitamin D3contained 50.4% less 25-[3H]hydroxyvitamin D3in treated rats given 1,25-dihydroxyvitamin D3than in those given only the vehicle. Further, 1,25-dihydroxyvitamin D3treatment had no effect onin vivodisappearance of 25-[3H]hydroxyvitamin D3. Taken together, these results demonstrate that the decrease in 25-hydroxyvitamin D3levels observed in 1,25-dihydroxyvitamin D3-treated rats results from a decrease in production and not an increase in the metabolic clearance of 25-[3H]hydroxyvitamin D3.