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 μg/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.