1,25-Dihydroxyvitamin D3 does not up-regulate vitamin D receptor messenger ribonucleic acid levels in hypophosphatemic mice.
The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) administration on duodenal vitamin D receptor (VDR) mRNA levels in hypophosphatemic (Hyp) mice, a murine homologue of human X-linked hypophosphatemic rickets, was examined. Basal levels of VDR mRNA in Hyp mice were similar to those of normal littermates and, in normal mice, VDR mRNA levels were up-regulated 1.8-2.7-fold after injection of 1 microgram/kg 1,25(OH)2D3. In contrast, no significant change in VDR mRNA was observed in Hyp mice treated with 1,25(OH)2D3. To determine the effect of phosphate repletion on VDR mRNA levels, high-phosphate diet was fed to Hyp mice. Although plasma phosphorus concentration was restored to normal, up-regulation of VDR mRNA was not recovered with phosphate supplementation. These results indicate that the vitamin D-resistance in Hyp mice is not caused by hypophosphatemia, per se, and may result from a fundamental molecular defect in vitamin D action at the intestine which could be related to ineffective up-regulation of VDR mRNA by 1,25(OH)2D3.
Nakajima
S
S
Department of Pediatrics, Osaka University School of Medicine, Japan.
Yamaoka
K
K
Okada
S
S
Pike
J W
JW
Seino
Y
Y
Haussler
M R
MR
D000818:Animals; D015152:Blotting, Northern; D002117:Calcitriol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism*; D007015:Hypophosphatemia, Familial / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000097:blood* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects*
D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol