Suppression of rat hepatic vitamin D-25-hydroxylase by cholecalciferol, but not by 25-hydroxy- or 1,25-dihydroxymetabolites.
Hepatic vitamin D-25-hydroxylase activity is greater in vitamin D-depleted than replete animals. We investigated whether vitamin D itself or a metabolite of vitamin D was responsible for modulating the activity of vitamin D-25-hydroxylase. Accordingly, we repleted vitamin D-depleted rats with subcutaneous injections of 2600, 520, and 130 pmoles of cholecalciferol (D3), 25-hydroxycholecalciferol (25(OH)D3), and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), respectively, for up to 3 weeks. Repletion resulted in accelerated weight gain and in increased activity of gut mucosal alkaline phosphatase. Using an improved assay to measure vitamin D-25-hydroxylase activity in liver homogenates, we found 78% reduction (P less than 0.001) in the D3-repleted group, maximal by 1 week, in contrast to no change in those groups treated with D3 metabolites. D3, 25(OH)D3, and D3-esters remaining in livers at the time of assay were estimated in a parallel experiment using [3H]D3-repleted rats. Residual D3 accounted for only a 9% dilution of substrate in the assay. 25(OH)D3 was present in the liver at concentrations two orders of magnitude lower than the amount required to inhibit vitamin D-25-hydroxylase activity in vitro. D3 esters had no inhibitory effect in vitro at 250-fold excess of that found in the repleted rat liver. Vitamin D appears to modulate its D-25-hydroxylase activity in biological systems by a mechanism other than feedback inhibition by 25(OH)D3, 1,25(OH)2D3, or D3-esters.
Bolt
M J
MJ
Clinical Nutrition Research Center, University of Chicago, Illinois.
Meredith
S C
SC
Rosenberg
I H
IH
D000818:Animals; D002112:Calcifediol / Q000032:analysis / Q000494:pharmacology*; D002117:Calcitriol / Q000032:analysis / Q000494:pharmacology*; D002762:Cholecalciferol / Q000032:analysis / Q000494:pharmacology* / Q000031:analogs & derivatives; D053493:Cholestanetriol 26-Monooxygenase; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D013250:Steroid Hydroxylases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000188:drug therapy
C033555:vitamin D3 palmitate; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D002117:Calcitriol; D002112:Calcifediol