{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:08:15Z","timestamp":1777918095181,"version":"3.51.4"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2008,12,19]],"date-time":"2008-12-19T00:00:00Z","timestamp":1229644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2008,12,19]],"date-time":"2008-12-19T00:00:00Z","timestamp":1229644800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron"],"abstract":"The low concentration of the biologically active metabolite of vitamin D, namely l\u03b1,25-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 [3H]-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 [3H]-1,25(OH)<sub>2<\/sub>D<sub>3<\/sub> binding capacity in short-term Nx (6-10 days after nephrectomy) was 663 \u00b1 114 fmol\/mg protein; it was 517 \u00b1 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 \u00b1 9 fmol\/mg protein) than in Intact (116 \u00b1 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 \u00b1 32 fmol\/mg protein versus 349 \u00b1 31 in Intact (n = 3, p < 0.01). Parathyroid VDR was 171 \u00b1 9 fmol\/mg protein in long-term Nx and 125 \u00b1 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 \u00b1 54 fmol\/mg protein versus 495 \u00b1 59 in intestinal mucosa, p < 0.05; 273 \u00b1 48 versus 104 \u00b1 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 \u00b1 0.06 pmol 24,25-dihydroxyvitamin D<sub>3<\/sub>\/mg protein) than in sham-operated normal rats (1.04 \u00b1 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.<\/jats:p>","DOI":"10.1159\/000189150","type":"journal-article","created":{"date-parts":[[2008,12,24]],"date-time":"2008-12-24T09:00:08Z","timestamp":1230109208000},"page":"619-628","source":"Crossref","is-referenced-by-count":9,"title":["Abnormal Expression and Regulation of Vitamin D Receptor in Experimental Uremia"],"prefix":"10.1159","member":"127","published-online":{"date-parts":[[2008,12,19]]},"container-title":["Nephron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/189150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000189150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:30:41Z","timestamp":1777660241000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000189150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000189150","archive":["Portico"],"relation":{},"ISSN":["1660-8151","2235-3186"],"issn-type":[{"value":"1660-8151","type":"print"},{"value":"2235-3186","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,19]]}}}