Expression of the renal 25-hydroxyvitamin D-24-hydroxylase gene: regulation by dietary phosphate.
1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] plays a key role in phosphate (Pi) homeostasis through its phosphatemic actions on intestine and bone. In turn, dietary Pi restriction increases serum 1,25(OH)2D3 by stimulating its production, but its effect on vitamin D catabolism is less clear. Here we have examined the effects of dietary Pi on the expression of the renal vitamin D-24-hydroxylase (24-OHase), the first enzyme in the catabolic pathway for vitamin D compounds. Rats fed a low Pi (0.02% P) diet showed a fivefold decrease in renal 24-OHase mRNA compared with rats fed a normal Pi (0.67% P) diet. 24-OHase mRNA and 24-OHase activity decreased within 24 h of Pi restriction, reached a minimum by 48 h, and remained low through 14 days. Decreased 24-OHase mRNA was observed with more moderate Pi restriction (0.2% P), but higher Pi (1.2% P) did not increase 24-OHase mRNA over the 0.8% P diet. 24-OHase mRNA correlated well with plasma Pi (r = 0.862, P < 0.001). In conclusion, renal 24-OHase expression is regulated by dietary phosphate at the mRNA level.
Wu
S
S
Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Finch
J
J
Zhong
M
M
Slatopolsky
E
E
Grieff
M
M
Brown
A J
AJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase