Abnormal regulation of renal vitamin D catabolism by dietary phosphate in murine X-linked hypophosphatemic rickets.
Hyp mice exhibit increased renal catabolism of vitamin D metabolites by the C-24 oxidation pathway (1988. J. Clin. Invest. 81:461-465). To examine the regulatory influence of dietary phosphate on the renal vitamin D catabolic pathway in Hyp mice, we measured C-24 oxidation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in renal mitochondria isolated from Hyp mice and normal littermates fed diets containing 0.03% (low-Pi), 1% (control-Pi), and 1.6% (high-Pi) phosphate. In normal mice the low-Pi diet led to a rise in serum 1,25(OH)2D (22.2 +/- 1.8 to 48.1 +/- 6.8 pg/ml, P less than 0.05) and no change in C-24 oxidation products (0.053 +/- 0.006 to 0.066 +/- 0.008 pmol/mg protein per min) when compared with the control diet. In Hyp mice the low-Pi diet elicited a fall in serum 1,25(OH)2D (21.9 +/- 1.2 to 8.0 +/- 0.2 pg/ml, P less than 0.05) and a dramatic increase in C-24 oxidation products (0.120 +/- 0.017 to 0.526 +/- 0.053 pmol/mg protein per min, P less than 0.05) when compared with the control diet. The high-Pi diet did not significantly alter serum levels of 1,25(OH)2D or C-24 oxidation products in normal mice. Hyp mice on the high-Pi diet experienced a rise in serum 1,25(OH)2D (21.9 +/- 1.2 to 40.4 +/- 7.3, P less than 0.05) and a fall in C-24 oxidation products (0.120 +/- 0.017 to 0.043 +/- 0.007 pmol/mg protein per min, P less than 0.05). The present results demonstrate that the defect in C-24 oxidation of 1,25(OH)2D3 in Hyp mice is exacerbated by phosphate depletion and corrected by phosphate supplementation. The data suggest that the disorder in vitamin D metabolism in the mutant strain is secondary to the perturbation in phosphate homeostasis.
Tenenhouse
H S
HS
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Jones
G
G
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism; D004032:Diet; D007015:Hypophosphatemia, Familial / Q000235:genetics / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D012016:Reference Values; D012279:Rickets / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*; D014960:X Chromosome
D010710:Phosphates; D014807:Vitamin D; D002117:Calcitriol; D002118:Calcium