Feedback regulation of vitamin D metabolism by 1,25 dihydroxy cholecalciferol

Many factors influence the production of 1,25(OH)₂D₃ (1,25-dihydroxycholecalciferol) by the kidney. One important factor seems to be feedback regulation by 1,25(OH)₂D₃ itself. Administration of 1,25(OH)₂D₃ to vitamin D-deficient chicks abolishes renal 25(OH)D₃(25-hydroxycholecalciferol)1-hydroxylase activity and induces the appearance of 25(OH)D₃ 24-hydroxylase activity. It is likely that these effects are mediated via a nuclear effect, as they are prevented by pretreatment with actinomycin D and α-amanitin. Further, 1,25(OH)₂D₃ has a marked effect on gene transcription in the kidney cell, as assessed by measurement of RNA polymerase activities. RNA polymerase I and II activities are 80-90% inhibited by 12.5 nmol of 1,25(OH)₂D₃ within 30 min of subcutaneous administration, indicating an immediate and massive decrease in total gene transcription. By 4h RNA polymerase II activity has returned to control values, but RNA polymerase I activity is markedly enhanced. These results are consistent with the view that regulation of cholecalciferol metabolism in the kidney is associated with an effect of the active metabolite on the kidney nucleus.