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Effects of the Administration of Phosphate on Nuclear 1,25-Dihydroxyvitamin D₃ Uptake by Duodenal Mucosal Cells of Hyp Mice

Department of Pediatrics, Osaka University School of Medicine Fukushima-ku, Osaka 553, Japan

Address requests for reprints to: Dr. Takehisa Yamamoto, Genetics Unit, Shriners Hospital for Crippled Children, 1529 Cedar Avenue, Montreal, Quebec, Canada H3G 1A6.

Abstract

Effects of the administration of phosphate on nuclear 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] uptake by duodenal mucosal cells of Hyp mice were investigated. In Hyp mice fed a high phosphate diet (1.1% Ca and 2.0% phosphate) for 2 weeks, maximal nuclear 1,25-(OH)₂D₃ binding by duodenal mucosal cells is significantly increased from 5.01 ± 0.49 x 103 to 8.23 ± 1.10 x 103 sites/cell (P < 0.05). No significant change was observed in normal mice fed the same diet. The serum phosphate concentration of Hyp mice increased significantly (P < 0.01), whereas no significant change was found in normal mice. On this regimen, serum calcium, urinary cAMP to creatinine ratio, and cytosolic 1,25-(OH)₂D₃ receptor number in Hyp mice were not changed significantly. On the basis of these data, we speculate that the recovery of serum phosphate in Hyp mice fed a high phosphate diet affects the recovery of nuclear 1,25- (OH)₂D₃ uptake by duodenal mucosal cells. The mechanism for this recovery is not related to either the secondary hyperparathyroidism or the change in cytosolic 1,25-(OH)₂D₃ receptor content but, rather, to increased binding of l,25-(OH)₂D₃-receptor complex to nuclei. Hypophosphatemia, therefore, appears to play a role in the vitamin D resistance in Hyp mice. (Endocrinology 122: 576–580, 1988)

Received November 14, 1986.