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Gene Review

Vdr  -  vitamin D (1,25- dihydroxyvitamin D3)...

Rattus norvegicus

Synonyms: 1,25-dihydroxyvitamin D3 receptor, Nr1i1, Nuclear receptor subfamily 1 group I member 1, VDR, Vitamin D3 receptor
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Disease relevance of Vdr


High impact information on Vdr

  • The results suggest that GHS rats hyperrespond to minimal doses of 1,25(OH)2D3 by an upregulation of VDR gene expression [5].
  • Administration of 1,25(OH)2D3 increased VDR gene expression significantly in GHS but not normocalciuric animals, in a time- and dose-dependent manner [5].
  • Under basal conditions, VDR mRNA levels in GHS rats were lower in duodenum and higher in kidney compared with wild-type controls [5].
  • Total RNAs were isolated from both duodenum and kidney cortex, and the VDR and calbindin mRNA levels were determined by Northern blot hybridization using specific cDNA probes [5].
  • Hypercalciuria in genetic hypercalciuric stone-forming (GHS) rats is accompanied by intestinal Ca hyperabsorption with normal serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, elevation of intestinal, kidney, and bone vitamin D receptor (VDR) content, and greater 1,25(OH)2D3-induced bone resorption in vitro [5].

Chemical compound and disease context of Vdr


Biological context of Vdr


Anatomical context of Vdr


Associations of Vdr with chemical compounds


Physical interactions of Vdr

  • Here, we have combined transient-overexpression, coimmunoprecipitation, in situ colocalization, chromatin immunoprecipitation, and glutathione S-transferase pull-down analyses to demonstrate that in osteoblastic cells expressing OC, VDR interacts directly with Runx2 bound to site B, which is located immediately adjacent to the VDRE [17].
  • 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 of sham-operated rats with normal kidney function (Intact) [18].
  • Scatchard analysis confirmed that TNF-alpha (100 ng/ml for 24 h) caused a decrease in the number of binding sites without change in VDR affinity [19].

Regulatory relationships of Vdr


Other interactions of Vdr

  • After 24 h the VDR mRNA level in PTH-treated cells returned to control level [14].
  • Kidney VDR mRNA relative to GAPDH mRNA correlated inversely with serum 1,25(OH)(2)D (r = -0.714, P = 0.006) [24].
  • The treatment with SDZ PSC 833 did not affect calbindin-D28k or VDR expression, but did cause a 73% decrease in 24-OHase mRNA levels [25].
  • This interaction contributes significantly to 1alpha,25-dihydroxyvitamin D3-dependent enhancement of the OC promoter and requires a region located C terminal to the runt homology DNA binding domain of Runx2 and the N-terminal region of VDR [17].
  • Using nephrectomized rats, we examined changes in mRNA levels of CYP27B1 (25-hydroxyvitamin D3-1 alpha-hydroxylase), CYP24 (25-hydroxyvitamin D3-24-hydroxylase), and vitamin D receptor in relation to megalin, recently found to participate in renal vitamin D metabolism [26].

Analytical, diagnostic and therapeutic context of Vdr


  1. Regulation of parathyroid vitamin D receptor expression by extracellular calcium. Garfia, B., Cañadillas, S., Canalejo, A., Luque, F., Siendones, E., Quesada, M., Almadén, Y., Aguilera-Tejero, E., Rodríguez, M. J. Am. Soc. Nephrol. (2002) [Pubmed]
  2. Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats. Shiizaki, K., Negi, S., Hatamura, I., Sakaguchi, T., Saji, F., Kunimoto, K., Mizobuchi, M., Imazeki, I., Ooshima, A., Akizawa, T. J. Am. Soc. Nephrol. (2005) [Pubmed]
  3. Persistent downregulation of calcium-sensing receptor mRNA in rat parathyroids when severe secondary hyperparathyroidism is reversed by an isogenic kidney transplantation. Lewin, E., Garfia, B., Recio, F.L., Rodriguez, M., Olgaard, K. J. Am. Soc. Nephrol. (2002) [Pubmed]
  4. 1,25-Dihydroxyvitamin D3 receptor-like macromolecule in rat osteogenic sarcoma cell lines. Manolagas, S.C., Haussler, M.R., Deftos, L.J. J. Biol. Chem. (1980) [Pubmed]
  5. Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats. Yao, J., Kathpalia, P., Bushinsky, D.A., Favus, M.J. J. Clin. Invest. (1998) [Pubmed]
  6. The roles of calcium and 1,25-dihydroxyvitamin D3 in the regulation of vitamin D receptor expression by rat parathyroid glands. Brown, A.J., Zhong, M., Finch, J., Ritter, C., Slatopolsky, E. Endocrinology (1995) [Pubmed]
  7. Vitamin D receptor stable transfection restores the susceptibility to 1,25-dihydroxyvitamin D3 cytotoxicity in a rat glioma resistant clone. Davoust, N., Wion, D., Chevalier, G., Garabedian, M., Brachet, P., Couez, D. J. Neurosci. Res. (1998) [Pubmed]
  8. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. Sawaya, B.P., Koszewski, N.J., Qi, Q., Langub, M.C., Monier-Faugere, M.C., Malluche, H.H. J. Am. Soc. Nephrol. (1997) [Pubmed]
  9. Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D3. Identification of a vitamin D-responsive element in the human NAPi-3 gene. Taketani, Y., Segawa, H., Chikamori, M., Morita, K., Tanaka, K., Kido, S., Yamamoto, H., Iemori, Y., Tatsumi, S., Tsugawa, N., Okano, T., Kobayashi, T., Miyamoto, K., Takeda, E. J. Biol. Chem. (1998) [Pubmed]
  10. The 1,25-dihydroxy-vitamin D3 receptor is phosphorylated in response to 1,25-dihydroxy-vitamin D3 and 22-oxacalcitriol in rat osteoblasts, and by casein kinase II, in vitro. Jurutka, P.W., Terpening, C.M., Haussler, M.R. Biochemistry (1993) [Pubmed]
  11. Functional cooperation between CCAAT/enhancer-binding proteins and the vitamin D receptor in regulation of 25-hydroxyvitamin D3 24-hydroxylase. Dhawan, P., Peng, X., Sutton, A.L., MacDonald, P.N., Croniger, C.M., Trautwein, C., Centrella, M., McCarthy, T.L., Christakos, S. Mol. Cell. Biol. (2005) [Pubmed]
  12. Evidence for a regulatory role of inducible cAMP early repressor in protein kinase a-mediated enhancement of vitamin D receptor expression and modulation of hormone action. Huening, M., Yehia, G., Molina, C.A., Christakos, S. Mol. Endocrinol. (2002) [Pubmed]
  13. Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro. Klaus, G., May, T., Hügel, U., von Eichel, B., Rodriguez, J., Fernandez, P., Reichrath, J., Ritz, E., Mehls, O. Kidney Int. (1997) [Pubmed]
  14. Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by parathyroid hormone and cAMP-agonists. van Leeuwen, J.P., Birkenhäger, J.C., Vink-van Wijngaarden, T., van den Bemd, G.J., Pols, H.A. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  15. DNA sequences in the rat parathyroid hormone-related peptide gene responsible for 1,25-dihydroxyvitamin D3-mediated transcriptional repression. Falzon, M. Mol. Endocrinol. (1996) [Pubmed]
  16. Transactivation of rat apical sodium-dependent bile acid transporter and increased bile acid transport by 1alpha,25-dihydroxyvitamin D3 via the vitamin D receptor. Chen, X., Chen, F., Liu, S., Glaeser, H., Dawson, P.A., Hofmann, A.F., Kim, R.B., Shneider, B.L., Pang, K.S. Mol. Pharmacol. (2006) [Pubmed]
  17. Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells. Paredes, R., Arriagada, G., Cruzat, F., Villagra, A., Olate, J., Zaidi, K., van Wijnen, A., Lian, J.B., Stein, G.S., Stein, J.L., Montecino, M. Mol. Cell. Biol. (2004) [Pubmed]
  18. Regulation of intestinal vitamin D receptor expression in experimental uraemia: effects of parathyroidectomy and administration of PTH. Szabó, A., Schmutz, A., Pesian, S., Schmidt-Gayk, H., Ritz, E., Reichel, H. Nephrol. Dial. Transplant. (1998) [Pubmed]
  19. Tumor necrosis factor alpha decreases 1,25-dihydroxyvitamin D3 receptors in osteoblastic ROS 17/2.8 cells. Mayur, N., Lewis, S., Catherwood, B.D., Nanes, M.S. J. Bone Miner. Res. (1993) [Pubmed]
  20. Regulation of renal vitamin D receptor is an important determinant of 1alpha,25-dihydroxyvitamin D(3) levels in vivo. Beckman, M.J., DeLuca, H.F. Arch. Biochem. Biophys. (2002) [Pubmed]
  21. The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine. Yamamoto, H., Miyamoto, K., Li, B., Taketani, Y., Kitano, M., Inoue, Y., Morita, K., Pike, J.W., Takeda, E. J. Bone Miner. Res. (1999) [Pubmed]
  22. Calmodulin-dependent kinase IV stimulates vitamin D receptor-mediated transcription. Ellison, T.I., Dowd, D.R., MacDonald, P.N. Mol. Endocrinol. (2005) [Pubmed]
  23. Vitamin D upregulates expression of ECaC1 mRNA in semicircular canal. Yamauchi, D., Raveendran, N.N., Pondugula, S.R., Kampalli, S.B., Sanneman, J.D., Harbidge, D.G., Marcus, D.C. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  24. Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth, R., Milojevic, S., Peltekova, V. J. Nutr. (2000) [Pubmed]
  25. Evidence for the impairment of the vitamin D activation pathway by cyclosporine A. Grenet, O., Bobadilla, M., Chibout, S.D., Steiner, S. Biochem. Pharmacol. (2000) [Pubmed]
  26. Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats. Takemoto, F., Shinki, T., Yokoyama, K., Inokami, T., Hara, S., Yamada, A., Kurokawa, K., Uchida, S. Kidney Int. (2003) [Pubmed]
  27. Expression of 25(OH)D3 24-hydroxylase in distal nephron: coordinate regulation by 1,25(OH)2D3 and cAMP or PTH. Yang, W., Friedman, P.A., Kumar, R., Omdahl, J.L., May, B.K., Siu-Caldera, M.L., Reddy, G.S., Christakos, S. Am. J. Physiol. (1999) [Pubmed]
  28. Immunohistochemical detection of 1,25-dihydroxyvitamin D receptor in rat vaginal epithelium. Yildirim, B., Abban, G., Erdogan, B.S. Fertil. Steril. (2004) [Pubmed]
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