IMPAIRED HOMOLOGOUS UP-REGULATION OF VITAMIN-D RECEPTOR IN RATS WITH CHRONIC-RENAL-FAILURE

We studied the homologous regulation of the vitamin D receptor (VDR) in the duodenum of rats with chronic renal failure. Mean basal nuclear H-3-labeled 1 alpha,25-dihydroxyvitamin D-3 {[H-3]1,25(OH)(2)D-3} binding capacity was 48 and 43 fmol/mg protein for sham-operated and uremic rats with similar dissociation constants (Ka), respectively. These results coincided with those of immunoblot analysis, which found that VDR protein level of uremic rats was 87.6% that of sham-operated rats. In uremic rats, 1,25(OH)(2)D-3, 2.0 mu g/kg, failed to upregulate VDR protein levels until 24 h, in contrast to the significant increases produced in sham-operated rats at both 12 (1.55-fold) and 24 h (1.75-fold). Baseline level of VDR mRNA in uremic rats, determined by Northern blot analysis, was comparable to that in sham-operated rats. Treatment with 1,25(OH)(2)D-3 slightly decreased VDR mRNA at 6-24 h in the sham-operated rats, in contrast to the increase seen at 6 h in uremic rats. These results suggest that the homologous upregulation of VDR was attenuated in rats with chronic renal failure because of an impairment at a translational and/or posttranslational step.