Influence of calcium or 1,25-dihydroxyvitamin D3 supplementation on the hepatic microsomal and in vivo metabolism of vitamin D3 in vitamin D-depleted rats.
Hypocalcemic vitamin D (D)-depleted rats were supplemented with calcium or 1,25(OH)2D3, and the metabolism of D3 to 25(OH)D3 was studied. Infusion with 7 or 65 pmol 1,25(OH)2D3 X 24 h-1 led to normal or slight hypercalcemia associated with physiological and supraphysiological plasma concentrations of the hormone while calcium supplementation normalized plasma calcium despite 1,25(OH)2D3 concentrations as low as those observed in hypocalcemic controls. Constant administrations of [14C]D3 during the supplementation regimens uncovered a stimulation of the in vivo 25(OH)D3 production by calcium supplementation; this was further confirmed in vitro by an increase in the hepatic microsomal D3-25 hydroxylase. The group supplemented with pharmacological doses of the hormone displayed lower circulating concentrations of both D3 and 25(OH)D3 while the in vitro 25(OH)D3 production remained unaffected by 1,25(OH)2D3. Investigation of the kinetics of intravenous 25(OH)[3H]D3 revealed similar elimination constants in all groups. The data indicate that calcium supplementation of hypocalcemic D-depleted rats results in an increased transformation of D3 into 25(OH)D3 while supplementation with 1,25(OH)2D3 does not affect the in vitro D3-25 hydroxylase but seems to influence the in vivo handling of the vitamin by accelerating its metabolism.
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002762:Cholecalciferol / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase; D005260:Female; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000032:analysis; D014808:Vitamin D Deficiency / Q000378:metabolism*
D002250:Carbon Radioisotopes; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D002117:Calcitriol; D002118:Calcium