Parathyroid hormone down-regulates 1,25-dihydroxyvitamin D receptors (VDR) and VDR messenger ribonucleic acid in vitro and blocks homologous up-regulation of VDR in vivo.
Parathyroid hormone down-regulates 1,25-dihydroxyvitamin D receptors (VDR) and VDR messenger ribonucleic acid in vitro and blocks homologous up-regulation of VDR in vivo.
复制标题
甲状旁腺激素在体外下调 1,25-二羟基维生素 D 受体 (VDR) 和 VDR 信使核糖核酸，并在体内阻断 VDR 的同源上调。
DOI：
10.1210/endo-127-2-942
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发表时间：
1990
期刊：
影响因子：
4.8
通讯作者：
R. L. Horst
中科院分区：
文献类型：
--
作者：
T. A. Reinhardt;R. L. Horst
1,25-二羟基维生素D3 [1,25(OH)2D3]是已知的1,25(OH)2D3受体（VDR）的体外和体内上调因子。然而，饮食缺钙引起的血浆1,25(OH)2D3升高5- 10倍并不导致肠道VDR上调，而导致肾脏VDR下调。在某些生理应激下，血浆PTH的增加先于血浆125 (OH)2D3的增加。因此，本研究在体外和体内分别对雄性Holtzman大鼠ROS 17/2.8细胞和PTH对VDR调节的影响进行了研究。用PTH （0-5 nM）处理ROS细胞导致VDR在暴露18 h时从95 +/- 9下降到35 +/- 5 fmol/mg蛋白，呈剂量和时间依赖性下降。PTH的ED50为1 nM。VDR蛋白的下降伴随着VDR信使RNA (mRNA) 50%的下降。经Scatchard分析，pth介导的VDR下调发生在不影响VDR对1,25(OH)2D3亲和力的情况下。此外，PTH对VDR调节的影响是特异性的，因为细胞糖皮质激素受体浓度不受PTH治疗的影响。在相应的实验中，1,25(OH)2[3H]D3处理ROS细胞可导致VDR和VDR mRNA表达增加3- 4倍。同时添加PTH和1,25(OH)2[3H]D3可抑制1,25(OH)2[3H]D3介导的VDR和VDR mRNA上调。同样，PTH也抑制维甲酸诱导的VDR和VDR mRNA的异源上调。在体内实验中，1,25(OH)2D3 （1.5 ng/h）灌胃5 d后，大鼠肠道VDR、肾脏VDR和肾脏24-羟化酶的表达分别增加了331%、336%和4000%。PTH （1.8 IU/h）与1,25(OH)2D3联合输注完全抑制了1,25(OH)2D3介导的肠道VDR和肾脏24-羟化酶的升高，并使1,25(OH)2D3介导的肾脏VDR上调减少了一半以上。这些数据表明，PTH是VDR的有效下调因子，PTH和125 (OH)2D3对某些基因的表达具有相反的作用。
1,25-Dihydroxyvitamin D3 [1,25(OH)2D3) is a known up-regulator of 1,25(OH)2D3 receptor (VDR) both in vitro and in vivo. However, a 5- to 10-fold increase in plasma 1,25(OH)2D3 induced by dietary calcium deficiency does not result in up-regulation of intestinal VDR, and kidney VDR is down-regulated. Under certain physiological stresses, an increase in plasma PTH precedes increased plasma 1,25(OH)2D3. Therefore, the present study examined the effect of PTH on VDR regulation in vitro in ROS 17/2.8 cells and in vivo in male Holtzman rats. Treatment of ROS cells with PTH (0-5 nM) resulted in a dose and time-dependent decline in VDR from 95 +/- 9 to 35 +/- 5 fmol/mg protein at 18 h of exposure. The ED50 for PTH was 1 nM. This decline in VDR protein was attended by a 50% decline in VDR messenger RNA (mRNA). The PTH-mediated down-regulation of VDR occurred without affecting the affinity of VDR for 1,25(OH)2D3 as determined by Scatchard analysis. Also, the effect of PTH on VDR regulation was specific since cell glucocorticoid receptor concentration was not affected by PTH treatment. In accompanying experiments, 1,25(OH)2[3H]D3 treatment of ROS cells was shown to result in a 3- to 4-fold increased expression of VDR and VDR mRNA. The simultaneous addition of PTH and 1,25(OH)2[3H]D3 resulted in inhibition of the 1,25(OH)2[3H]D3-mediated up-regulation of VDR and VDR mRNA. Similarly, PTH also inhibited heterologous up-regulation of VDR and VDR mRNA induced by retinoic acid. In in vivo experiments, rats infused for 5 days with 1,25(OH)2D3 (1.5 ng/h) increased their expression of intestinal VDR, kidney VDR, and kidney 24-hydroxylase by 31, 336, and 4000%, respectively. Coinfusion of PTH (1.8 IU/h) along with 1,25(OH)2D3 completely inhibited the 1,25(OH)2D3-mediated increases in intestinal VDR and kidney 24-hydroxylase and reduced the 1,25(OH)2D3-mediated up-regulation of kidney VDR by more than half. These data suggest that PTH is a potent down-regulator of VDR and that PTH and 1,25(OH)2D3 have opposing effects on the expression of certain genes.