In vivo and in vitro inhibition of rat liver vitamin D3-25-hydroxylase activity by 19-hydroxy-10(S),19-dihydrovitamin D3.
Rats treated with varying amounts of 19-hydroxy-10(S),19-dihydrovitamin D3 prior to administration of physiologic doses of vitamin D3 exhibit normal intestinal calcium transport but are unable to mobilize bone calcium. In contrast, 19-hydroxy-10(R),19-dihydrovitamin D3 had no inhibitory activity. Circulating serum levels of 25-hydroxy[3H]vitamin D3 and 1 alpha, 25-dihydroxy[3H]vitamin D3 are markedly suppressed but not totally eliminated in animals predosed with 19-hydroxy-10(S),19-dihydrovitamin D3 before [3H]vitamin D3. Hepatic 25-hydroxy[3H]vitamin D3 levels were approximately equal in both 19-hydroxy-10(S),19-dihydroviotamin D3 treated and untreated rats. However, the rate of conversion of [3H]vitamin D3 to 25-hydroxyvitamin D3 in vivo is greatly reduced in the treated rats. The inhibitory vitamin analogue was also show to block hepatic microsomal 25-hydroxylation in vitro. These results indicate that 19-hydroxy-10(S),19-dihydrovitamin D3 is a specific inhibitor for a hepatic microsomal vitamin D3-25-hydroxylase system.
D000818:Animals; D001692:Biological Transport; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000172:deficiency / Q000378:metabolism; D002762:Cholecalciferol / Q000502:physiology; D053493:Cholestanetriol 26-Monooxygenase; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D014808:Vitamin D Deficiency / Q000378:metabolism
D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; C028335:19-hydroxy-10(S),19-dihydrovitamin D3; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D002118:Calcium