Nephrology Dialysis Transplantation, Vol 13, Issue 2 338-347, Copyright © 1998 by Oxford University Press
A Szabo, A Schmutz, S Pesian, H Gayk, E Ritz and H Reichel
In this study, the effects of PTH on binding of
[3H]-1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and on
vitamin D receptor (VDR) mRNA concentration were assessed in intestinal
mucosa of subtotally nephrectomized rats (Nx) and in intestinal mucosa
sham-operated rats with normal kidney function (Intact). Intestinal
1,25(OH)2D3 binding capacity of Intact remained unchanged (I) after
parathyroidectomy (PTx), (ii) after administration of PTH for up to 6 days,
and (iii) after PTx and subsequent administration of PTH
(n=4 experiments). In contrast, PTx of subtotally
nephrectomized animals (Nx-PTx) decreased 1,25(OH)2D3 binding capacity from
757±95 fmol/mg protein in Nx to 417±42 in Nx-PTx
(P<0.01, n=5). PTH
administration had no effect on intestinal 1,25(OH)2D3 binding capacity in
Nx. However, PTH administration to Nx-PTx resulted in re-elevation of
1,25(OH)2D3 binding capacity to a level (790±113 fmol/mg
protein) which was comparable to Nx. Kd-values
remained unaltered under all experimental conditions. The intestinal VDR
mRNA concentration (normalized to {beta}-actin mRNA) was decreased, on
average, by 23% in Nx-PTx (P<0.05
versus Nx). In further experiments, 1,25(OH)2D3 was
administered to Nx-PTx. This resulted in upregulation of 1,25(OH)2D3
binding capacity as compared to vehicle-treated Nx-PTx (562±90
fmol/mg protein versus 249±32,
P<0.01). The latter results could indicate that
PTH-mediated stimulation of residual renal 1,25(OH)2D3 production was
involved in PTH-mediated up-regulation of intestinal 1,25(OH)2D3 binding
capacity in Nx-PTx. To rule out this possibility, PTH was administered to
totally nephrectomized and parathyroidectomized rats (TNx-PTx). Since PTH
caused an approximately 80% increase (P<0.05)
in intestinal 1,25(OH)2D3 binding capacity under those experimental
conditions a mediator role of 1,25(OH)2D3 could be excluded. Functional
significance of decreased intestinal 1,25(OH)2D36 binding capacity in
Nx-PTx as compared to Nx was demonstrated by significantly lower
1,25(OH)2D3-mediated stimulation of intestinal 25(OH)2D3-24-hydroxylase
activity in Nx-PTx (209±68 pmol/mg protein) than in Nx
(385±81, P<0.01). The modulation of
intestinal 1,25(OH)2D3 binding capacity was not correlated with changes in
calcium, phosphate or 1,25(OH)2D3 serum concentrations under our
experimental conditions. Taken together, intact parathyroid gland function
was required to maintain adequate intestinal VDR expression in experimental
uraemia (but not in normal animals). The mechanism of the modulation of
intestinal VDR by PTH remains to be elucidated although an indirect effect
of PTH on VDR expression in intestinal mucosa seems most likely.
Keywords: calcium metabolism; vitamin D receptor;
uraemia; parathyroid hormone; vitamin D
ORIGINAL ARTICLES
Regulation of intestinal vitamin D receptor expression in experimental uraemia: effects of parathyroidectomy and administration of PTH
Department of Internal Medicine, Division of Nephrology, University of Heidelberg, Germany; 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary; Present address: Endocrine Laboratory, Im Breitspiel 15, D-69120 Heidelberg, Germany; Corresponding author address: Dialysis Centre, Schramberger Str. 28, D-78054-VS-Schwenningen, Germany
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