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Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat.
J Bone Miner Res 1995; 10(2):271-80JB

Abstract

Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50-100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1-10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 +/- 0.19 mg/dl (mean +/- SE) to 4.98 +/- 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 +/- 0.09 mg/dl to 11.63 +/- 0.15, 12.17 +/- 0.15, and 12.39 +/- 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)2D3 rapidly increased from 123 +/- 5.4 pg/ml to 304 +/- 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 +/- 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 +/- 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 +/- 141.88 fmol/mg of protein by D3 (n = 6; p < 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p < 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined.

Authors+Show Affiliations

Department of Medicine, University of Chicago Pritzker School of Medicine, Illinois, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7754807

Citation

Sriussadaporn, S, et al. "Tissue Specificity and Mechanism of Vitamin D Receptor Up-regulation During Dietary Phosphorus Restriction in the Rat." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 10, no. 2, 1995, pp. 271-80.
Sriussadaporn S, Wong MS, Pike JW, et al. Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat. J Bone Miner Res. 1995;10(2):271-80.
Sriussadaporn, S., Wong, M. S., Pike, J. W., & Favus, M. J. (1995). Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 10(2), pp. 271-80.
Sriussadaporn S, et al. Tissue Specificity and Mechanism of Vitamin D Receptor Up-regulation During Dietary Phosphorus Restriction in the Rat. J Bone Miner Res. 1995;10(2):271-80. PubMed PMID: 7754807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat. AU - Sriussadaporn,S, AU - Wong,M S, AU - Pike,J W, AU - Favus,M J, PY - 1995/2/1/pubmed PY - 1995/2/1/medline PY - 1995/2/1/entrez SP - 271 EP - 80 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 10 IS - 2 N2 - Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50-100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1-10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 +/- 0.19 mg/dl (mean +/- SE) to 4.98 +/- 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 +/- 0.09 mg/dl to 11.63 +/- 0.15, 12.17 +/- 0.15, and 12.39 +/- 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)2D3 rapidly increased from 123 +/- 5.4 pg/ml to 304 +/- 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 +/- 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 +/- 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 +/- 141.88 fmol/mg of protein by D3 (n = 6; p < 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p < 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/7754807/Tissue_specificity_and_mechanism_of_vitamin_D_receptor_up_regulation_during_dietary_phosphorus_restriction_in_the_rat_ L2 - https://doi.org/10.1002/jbmr.5650100214 DB - PRIME DP - Unbound Medicine ER -