Sriussadaporn S, Wong M S, Pike J W, Favus M J
Department of Medicine, University of Chicago Pritzker School of Medicine, Illinois, USA.
J Bone Miner Res. 1995 Feb;10(2):271-80. doi: 10.1002/jbmr.5650100214.
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.
饮食中磷的限制可上调肠道维生素D受体（VDR），但其上调的组织特异性以及受体积累的机制尚不清楚。因此，研究了低磷饮食（LPD）对肠道、肾脏和脾脏单核细胞/巨噬细胞中VDR含量的影响。体重50 - 100克的雄性Sprague-Dawley大鼠先喂食正常饮食（NPD；0.6%钙，0.65%磷）作为对照，然后喂食LPD（0.6%钙，0.1%磷）1 - 10天（第1天至第10天）。到第1天，LPD迅速将血清磷水平从11.11±0.19毫克/分升降至4.98±0.37毫克/分升（n = 9）。LPD使总血清钙分别在第1天、第2天和第3天从10.54±0.09毫克/分升升至11.63±0.15、12.17±0.15和12.39±0.18毫克/分升，然后保持稳定。血清1,25-(OH)2D3在第1天迅速从123±5.4皮克/毫升升至304±35皮克/毫升，到第5天达到平台期，然后在第10天逐渐升至464.9±27.7皮克/毫升。通过配体结合测定法测定的肠道VDR从喂食NPD的大鼠（n = 12）中每毫克胞浆蛋白169.6±13.7飞摩尔增加3.5倍，在第3天达到每毫克蛋白588.3±141.88飞摩尔的峰值（n = 6；p < 0.001），然后在第5天至第10天降至比NPD高2.5倍的平台水平（p < 0.05）。相比之下，LPD并未上调肾脏或脾脏单核细胞/巨噬细胞的VDR。Northern印迹分析显示，LPD第2天（n = 3）时肠道VDR mRNA增加2倍，然后在第5天后逐渐降至对照水平。相比之下，在磷限制的前5天肾脏VDR mRNA水平未发生变化，随后降至NPD对照的50%。这些研究结果表明，饮食中磷限制期间VDR的上调具有组织特异性，且上调机制具有时间依赖性。急性（第1天至第5天）磷限制通过增加VDR基因表达上调肠道VDR，而慢性（第5天至第10天）磷限制似乎通过与延长受体半衰期一致的非基因组机制改变VDR代谢。磷限制期间VDR组织特异性调节的本质仍有待确定。
