title: In vitro regulation of kidney 25-hydroxyvitamin D3-hydroxylase enzyme activities by vitamin D3 metabolites. Molecular specificity and mechanism of action.
abstract: An acute chick kidney tubule model was used to evaluate the molecular specificity of steroids which act to inhibit kidney 25-hydroxyvitamin D3-1-hydroxylase and induce 25-hydroxyvitamin D3-24-hydroxylase enzyme activities. Such hydroxylase-regulatory activity was confined to the vitamin D family of secosteroids. Vitamin D3 per se was not active. Rather, expression of hydroxylase-regulatory activity required acquisition of a C-25 hydroxyl grouping. Of the metabolites tested, 25-hydroxyvitamin D3 demonstrated the greatest hydroxylase-regulatory activity. Metabolites of 25-hydroxyvitamin D3 which contained hydroxyl groups at carbon atoms 1, or 24, or both, were also active in regulating the kidney hydroxylase enzymes. The hydroxylase-regulatory action of 1,25-dihydroxyvitamin D3 was blocked by inhibitors of RNA or protein synthesis, implicating a requirement for de novo protein synthesis. It was suggested that the regulatory process involves both hydroxylase-enzyme synthesis and turnover as well as enzyme-level modulation of endogenous enzyme activities.
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D013256:Steroids; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase