Effect of dietary calcium or phosphorus restriction and 1,25-dihydroxyvitamin D administration on rat intestinal 24-hydroxylase.
1,25-Dihydroxyvitamin D-24-hydroxylase (24-hydroxylase) modulates the biological effects of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in tissues. The presence of 24-hydroxylase in intestinal mucosa and the mass of the intestine suggest that the intestine is a major site of catabolism of 1,25-(OH)2D. How intestinal levels of 24-hydroxylase are regulated under various dietary conditions, such as calcium (Ca) or phosphorus (P) restriction, is poorly understood. In a series of trials on weanling and mature rats, the effects of dietary Ca or P restriction were compared with the effects of exogenous 1,25-(OH)2D3 administration on intestinal 24-hydroxylase activity. Exogenous administration of 1,25-(OH)2D3, by single bolus injection or constant infusion, increased intestinal 24-hydroxylase activity significantly. Dietary Ca and P restriction both resulted in increased plasma 1,25-(OH)2D3 concentrations several-fold above control rat values (P less than 0.001) and to levels higher than those achieved by constant infusion of 1.3 ng 1,25-(OH)2D3/h. Dietary Ca restriction increased intestinal 24-hydroxylase 6- to 20-fold above that of rats fed a Ca-replete diet (P less than 0.001). Dietary P restriction had no significant effect on intestinal 24-hydroxylase activity. These data suggest that dietary Ca restriction results in increased plasma levels of 1,25-(OH)2D3, which, in turn, leads to up-regulation of intestinal 24-hydroxylase. Conversely, dietary P restriction prevents 1,25-(OH)2D3-mediated up-regulation of 24-hydroxylase.
Goff
J P
JP
Agricultural Research Service, National Animal Disease Center, Ames, Iowa 50010-0070.
Reinhardt
T A
TA
Engstrom
G W
GW
Horst
R L
RL
D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D002118:Calcium / Q000008:administration & dosage*; D003577:Cytochrome P-450 Enzyme System; D004032:Diet; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010758:Phosphorus / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D010758:Phosphorus; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D002118:Calcium