Effect of 1,25-dihydroxyvitamin D3 on phosphate homeostasis in the X-linked hypophosphatemic (Hyp) mouse

We studied the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on homeostasis of inorganic phosphate (Pi) in murine hypophosphatemia (Hyp), a homologue of X-linked hypophosphatemia (XLH) in man. Normal mice given 1,25-(OH)2D3 (83 pg/g.d) by continuous subcut, infusion x 10 d) had a significant rise in plasma calcium (Ca) (p less than 0.001), plasma Pi (p less than 0.025) and fractional Ca excretion (p less than 0.001), without change in fractional Pi excretion or Na+-stimulated Pi transport in purified renal brush-border membrane vesicles (BBMV). Hyp littermates did not respond to this dose of 1,25-(OH)2D3. At 415 pg/g.d, Hyp mice had increased plasma Ca (p less than 0.001), fractional Ca excretion (p less than 0.001), and plasma Pi (p less than 0.001) but no change in either fractional Pi excretion or Na+-stimulated Pi transport in BBMV. At this dose, 1,25-(OH)2D3 also stimulated Pi transport by everted sacs of Hyp small intestine (p less than 0.001). No deficiency of Pi transport was found in untreated Hyp intestine. We conclude that 1,25-(OH)2D3 improves Pi homeostasis in the Hyp phenotype by its effect on intestine; the defect in renal Pi reabsorption remains unchanged.