Abnormal relationship between serum phosphate concentration and renal 25-hydroxycholecalciferol-1-alpha-hydroxylase...

C57BL/6J Hyp/Y mice (Hyp-mice, X-linked hypophosphatemic mice) were fed diets containing various concentrations of phosphate and calcium to produce serum phosphate concentrations from very low to normal. We measured the renal 25-OHD3-1 alpha-hydroxylase activity and compared it to that of C57BL/6J normal male mice. The enzyme activity in control diet Hyp-mice was not different from that in control diet normal mice, but it was considerably lower than that in hypophosphatemic normal mice. In spite of a very low serum phosphate concentration, 25-OHD3-1 alpha-hydroxylase activity was reduced in the low-phosphate diet Hyp-mice. In order to normalize serum phosphate concentration without decreasing the serum calcium concentrations, Hyp-mice were fed a high-phosphate and high-calcium diet. In this situation the enzyme activity was stimulated and was significantly higher than that of control diet normal mice and was also significantly increased compared to that of high-phosphate diet Hyp-mice, which had a hypocalcemia. Our data show that there is a positive correlation between the serum phosphate concentration and renal 25-OHD3-1 alpha-hydroxylase activity in Hyp-mice, which is opposite to the negative correlation between serum phosphate and 25-OHD3-1 alpha-hydroxylase present in normal mice. This supports the concept of deranged control of renal vitamin D metabolism in hypophosphatemic rickets.