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Evidence that low plasma 1,25‐dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X‐linked hypophosphatemic mice
Author(s) -
Meyer Ralph A.,
Meyer Martha H.,
Gray Richard W.,
Bruns M. Elizabeth
Publication year - 1987
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650020111
Subject(s) - medicine , endocrinology , chemistry , calcium , vitamin d and neurology , calcium metabolism , malabsorption , hypophosphatemia , vitamin , biology
X‐linked hypophosphatemic ( Hyp ) mice are a model for human sex‐linked vitamin D‐resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH) 2 vitamin D 3 , this hormone was continually infused via osmotic minipumps into 4‐week‐old normal and Hyp mice at 0,17, 50 or 150 ng/kg/day. After 3 days, 45 Ca and inorganic 32 P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45 Ca and 32 P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D‐dependent calcium‐binding protein (calbindin‐D 9K ; CaBP). Plasma 1,25(OH) 2 D was measured in these mice. There were significant correlations of plasma 1,25(OH) 2 D to the intestinal absorption of 45 Ca and 32 P and to duodenal and renal CaBP. Plasma 1,25(OH) 2 D was also measured in stock normal and Hyp mice and was found to be lower in 4‐week‐old Hyp mice than in 4‐week‐old normal mice (113 ± 10 p M ( n = 18) vs. 67 ± 10 ( n = 20), normal vs. Hyp, p < .01), but unchanged at 13 weeks of age (77 ± 13 ( n = 13) vs. 70 ± 15 ( n = 15), NS). This observed difference in plasma 1,25(OH) 2 D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal‐to‐ Hyp differences in intestinal absorption of 45 Ca and duodenal and renal CaBP. It also explained 72 ± 18% of the observed difference in 32 P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH) 2 D and that the lower plasma 1,25(OH) 2 D of 4‐week‐old Hyp mice causes intestinal malabsorption of calcium and phosphate.