1,25 dihydroxyvitamin D-induced inhibition of 3H-25 hydroxyvitamin D production by the rachitic rat liver in vitro.

The effect of the vitamin D metabolites 1,25 dihydroxyvitamin D (100 pg/ml) and 25-hydroxyvitamin D (30 ng/ml) on hepatic production of 3H-25 hydroxyvitamin D was investigated using rachitic liver perfusions and homogenates. 1,25 dihydroxyvitamin D inhibited hepatic 3H-25 hydroxyvitamin D production in the liver perfusion (3.6 +/- 0.4 vs 2.0 +/- 0.5 pmol/liver, P less than 0.05) and in liver homogenates (11.9 +/- 0.6 vs 10.1 +/- 0.4 pmol/g liver protein/3 h, P less than 0.02). Inhibition was time and dose dependent. 25-hydroxyvitamin D inhibited production in liver homogenates (11.9 +/- 0.6 vs 9.2 +/- 0.1 pmol/g liver protein/3 h, P less than 0.05) but not in the intact liver (3.6 +/- 0.4 vs 3.4 +/- 0.5 pmol/liver). The data indicate that 1,25 dihydroxyvitamin D is able to feedback regulate the production of its precursor, 25-hydroxyvitamin D. Although 25-hydroxyvitamin D also inhibits its own production in liver homogenates, it failed to alter total production in the intact liver, suggesting that this metabolite may require immediate access to the vitamin D 25-hydroxylase, located on the microsomes and mitochondria, to induce inhibition.