Abnormal 24-hydroxylation of 25-hydroxyvitamin d in the x-linked hypophosphatemic mouse

The effect of extracellular phosphate on the control of 25-hydroxyvitamin D₃ 24-hydroxylase was studied in normal mice and littermates with X-linked hypophosphatemic rickets (Hyp). 24-Hydroxylase activity and plasma concentrations of 24, 25-dihydroxyvitamin D₃ were significantly higher in Hyp mice than in normal mice when both groups were fed a normal diet containing 1.22% calcium (Ca) and 0.8% phosphorus (Pi). The differential in 24-hydroxylase activity was exaggerated when serum phosphate was reduced in normal mice by means of a low Pi diet or increased in Hyp mice by means of a high Pi diet. Differences in 24-hydroxylase activity between the two groups of mice were also demonstrated in the presence of varying Pi concentrations in vitro. Thus, in both Hyp and normal mice, 24-hydroxylase activity is influenced in a qualitatively similar manner by serum Pi. Plasma concentrations of 1, 25-dihydroxyvitamin D₃ were the same in normal and Hyp mice. The data are consistent with the hypothesis that control of the renal metabolism of 25-hydroxyvitamin D₃ in Hyp mice is reset such that 24-hydroxylase activity is inappropriately high for the prevailing serum phosphate over a wide range of concentrations.