Blog
About

0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Abnormal Expression and Regulation of Vitamin D Receptor in Experimental Uremia

      Nephron

      S. Karger AG

      Experimental uremia, Calcium metabolism, Vitamin D receptor, 1,25-Dihydroxyvitamin D3 , Regulation

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The low concentration of the biologically active metabolite of vitamin D, namely lα,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>), is critical to the pathogenesis of secondary hyperparathyroidism in chronic renal failure. The actions of 1,25(OH)<sub>2</sub>D<sub>3</sub> are mediated through binding to a cellular receptor protein, the vitamin D receptor (VDR). In order to further investigate expression and regulation of VDR in uremia, we measured specific [<sup>3</sup>H]-1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity and VDR mRNA concentration in intestinal mucosa and in parathyroid glands of subtotally nephrectomized rats (Nx) and compared Nx to sham-operated rats with normal kidney function (Intact). Intestinal [<sup>3</sup>H]-1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity in short-term Nx (6-10 days after nephrectomy) was 663 ± 114 fmol/mg protein; it was 517 ± 34 in Intact (p = 0.06, n = 6 experiments). Intestinal VDR mRNA concentration was comparable between Nx and Intact. Specific 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity in parathyroid glands was higher in Nx (195 ± 9 fmol/mg protein) than in Intact (116 ± 14 fmol/mg protein, n = 5, p < 0.05). The affinity of the VDR for l,25(OH)<sub>2</sub>D<sub>3</sub> (KD) did not change in Nx. The 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity in intestinal mucosa of more long-term uremic animals (14-16 weeks after subtotal Nx) was 519 ± 32 fmol/mg protein versus 349 ± 31 in Intact (n = 3, p < 0.01). Parathyroid VDR was 171 ± 9 fmol/mg protein in long-term Nx and 125 ± 3 in Intact (p < 0.01). These results were confirmed when 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity in uremic rats with hereditary polycystic kidney disease was compared to control rats with normal kidney function (757 ± 54 fmol/mg protein versus 495 ± 59 in intestinal mucosa, p < 0.05; 273 ± 48 versus 104 ± 27 in parathyroid glands, p < 0.05). In parallel to changes in intestinal 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity, 1,25(OH)<sub>2</sub>D<sub>3</sub>-mediated stimulation of intestinal 25(OH)D<sub>3</sub>-24-hydroxylase activity was significantly higher in long-term subtotally Nx (1.43 ± 0.06 pmol 24,25-dihydroxyvitamin D<sub>3</sub>/mg protein) than in sham-operated normal rats (1.04 ± 0.10, p < 0.05). Administration of 1,25(OH)<sub>2</sub>D<sub>3</sub> to sham-operated normal rats resulted in an increase of 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity by 20-40% in intestinal mucosa and by 40-50% in parathyroid glands. In contrast, 1,25(OH)<sub>2</sub>D<sub>3</sub> caused down-regulation of mean 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity in short-term Nx by 38% in intestinal mucosa (p < 0.01) and by 43% in parathyroid glands (p < 0.01). In long-term Nx, mean 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity was reduced by 20% in intestinal mucosa (p < 0.05) and by 22% in parathyroid glands (p < 0.01). After prolonged exposure to 1,25(OH)<sub>2</sub>D<sub>3</sub> for 6 weeks, intestinal 1,25(OH)<sub>2</sub>D<sub>3</sub> binding capacity was markedly down-regulated in uremic rats (43% versus vehicle-treated animals, p < 0.05). Taken together, our results provide evidence for abnormal expression and regulation of VDR in experimental uremia. This may be relevant for responsiveness to 1,25(OH)<sub>2</sub>D<sub>3</sub> in renal insufficiency.

          Related collections

          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1996
          1996
          19 December 2008
          : 73
          : 4
          : 619-628
          Article
          189150 Nephron 1996;73:619–628
          10.1159/000189150
          8856261
          © 1996 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 10
          Categories
          Original Paper

          Comments

          Comment on this article