Decreased nuclear uptake of 1,25-dihydroxyvitamin D3 by duodenal mucosal cells in the X-linked hypophosphatemic mouse.
We have shown that there is a significant decrease in the nuclear uptake of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by duodenal mucosal cells in the X-linked hypophosphatemic (Hyp) mouse. Duodenal mucosal cells prepared from control and Hyp mice were incubated with 1,25(OH)2[26,27-methyl-3H]D3 ([3H]-1,25(OH)2D3) for 30 min. to evaluate the time-course and perform saturation analysis. The results of time-course studies showed that saturation was attained in 30 min., reaching an average nuclear uptake of 10.4 fmol/tube in the control mice and 6.1 fmol/tube in the Hyp mice. The results of Scatchard analyses were as follows: dissociation constant (Kd) 5.71 X 10(-10) M and maximal binding sites 7.31 X 10(4) sites/cell in the control mice, and Kd 2.92 X 10(-10) M and maximal binding sites 4.88 X 10(4) sites/cell in the Hyp mice, the maximal binding sites of the latter showed a significant decrease (P less than 0.05) by Student's t test. In addition, there was no significant difference in the binding of [3H]-1,25(OH)2D3 to its residual cytosol receptors between the control and Hyp mice. On the basis of these data, we speculate that the reported resistance of Hyp mice to vitamin D may be due to decreased nuclear uptake of 1,25(OH)2D3 by their duodenal mucosal cells.
D000818:Animals; D001692:Biological Transport; D002117:Calcitriol / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol