Induction of vitamin D 24-hydroxylase messenger RNA and activity by 22-oxacalcitriol in mouse kidney and duodenum. Possible role in decrease of plasma 1 alpha,25-dihydroxyvitamin D3.
The synthetic analog of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 22-oxacalcitriol (OCT), retains most of the properties of 1,25(OH)2D3 but exhibits much less hypercalcemic action than the parent compound. The effects of OCT on plasma calcium, phosphorus, and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] concentrations were examined in mice. Administration of a single dose (24 pmol/g body wt, i.p.) of OCT had no effect on plasma calcium for up to 48 hr, significantly increased plasma phosphorus at 4 and 8 hr and significantly reduced the concentration of 1,25(OH)2D in plasma between 4 and 48 hr. Both OCT and 1,25(OH)2D3 at 24 pmol/g body wt (i.p.) induced a single, 3.4-kb mRNA encoding vitamin D 24-hydroxylase (24-OHase), the cytochrome P450 enzyme responsible for 1,25(OH)2D3 degradation, in kidney and duodenum. The OCT-induced increase in 24-OHase mRNA and an increase in enzyme activity were marked at 2 and 4 hr in both tissues. In kidney, mRNA abundance had decreased by 8 hr but remained above basal values for up to 30 hr; activity remained relatively high for up to 48 hr. In duodenum, 24-OHase mRNA abundance returned virtually to control values by 8 hr after OCT treatment; activity remained at nearly maximal levels for up to 30 hr but was decreased at 48 hr. The effects of OCT and 1,25(OH)2D3 on 24-OHase mRNA abundance and enzyme activity were dose-dependent in kidney and duodenum. Whereas the dose-response relations for the effects of both compounds on 24-OHase mRNA were similar, OCT was slightly more potent than 1,25(OH)2D3 in stimulating 24-OHase activity in both tissues. These results suggest that the OCT-induced decrease in plasma 1,25(OH)2D3 is attributable, at least in part, to an increased degradation of 1,25(OH)2D3, which results from an increase in 24-OHase abundance and enzyme activity.
Akeno
N
N
Department of Biochemistry, Ohu University School of Dentistry, Koriyama, Japan.
Saikatsu
S
S
Kimura
S
S
Horiuchi
N
N
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D003577:Cytochrome P-450 Enzyme System; D004386:Duodenum / Q000187:drug effects* / Q000201:enzymology; D004790:Enzyme Induction; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D010758:Phosphorus / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D010758:Phosphorus; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium