AJP - Renal Physiology, Vol 266, Issue 5 706-F712, Copyright © 1994 by American Physiological Society
Impaired homologous upregulation of vitamin D receptor in rats with chronic renal failure
H. Koyama, Y. Nishizawa, M. Inaba, M. Hino, J. M. Prahl, H. F. DeLuca and H. Morii
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
We studied the homologous regulation of the vitamin D receptor (VDR) in the
duodenum of rats with chronic renal failure. Mean basal nuclear 3H-labeled
1 alpha,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) binding capacity was 48
and 43 fmol/mg protein for sham-operated and uremic rats with similar
dissociation constants (Kd), 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)2D3, 2.0
micrograms/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)2D3 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.
