Inhibition of 25-hydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3 in rats

The regulation of the hepatic vitamin D-3 25-hydroxylase enzyme system by 1,25-dihydroxyvitamin D-3 was examined using male rats. Circulating 25-hydroxyvitamin D-3 levels decreased in response to increasing doses of 1,25-dihydroxyvitamin D-3 as determined by HPLC and serum protein binding assay. A maximum reduction in serum 25-hydroxyvitamin D-3 of 57.7% was achieved by the administration of 1,25-dihydroxyvitamin D-3 and higher doses produced no further reduction. The in vitro rate of vitamin D 25-hydroxylation by liver homogenates from rats given 1,25-dihydroxyvitamin D-3 was also reduced by 60.4%. Whole rat extracts from animals given [H-3]vitamin D-3 contained 50.4% less 25-[H-3]hydroxyvitamin D-3 in treated rats given 1,25-dihydroxyvitamin D, than in those given only the vehicle. Further, 1,25-dihydroxyvitamin D-3 treatment had no effect on in vivo disappearance of 25-[H-3]hydroxyvitamin D-3. Taken together, these results demonstrate that the decrease in 25-hydroxyvitamin D-3 levels observed in 1,25-dihydroxyvitamin D-3-treated rats results from a decrease in production and not an increase in the metabolic clearance of 25-[H-3]hydroxyvitamin D-3. (C) 1998 Academic Press.