Induction of the vitamin D 24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 is regulated by parathyroid hormone in UMR106 osteoblastic cells
Induction of the vitamin D 24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 is regulated by parathyroid hormone in UMR106 osteoblastic cells
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DOI：
10.1210/en.139.8.3375
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发表时间：
1998-08-01
期刊：
影响因子：
4.8
通讯作者：
Kumar, VB
中科院分区：
文献类型：
--
作者：
Armbrecht, HJ;Hodam, TL;Kumar, VB
维生素 D 24-羟化酶的表达在 1,25-二羟基维生素 D-3 (1, 25(OH)(2)D) 的靶组织中受到高度调节，可调节 1,25(OH)(2)D 的作用。在 UMR106 成骨细胞中，1,25(OH)(2)D 和 PTH 协同诱导 24-羟化酶表达。这些研究的目的是表征 1,25(OH)(2)D 和 PTH 之间在 24-羟化酶 (CYP24) 细胞色素 P450 成分的信使 RNA (mRNA) 水平方面的相互作用。单独的 PTH 对 CYP24 mRNA 水平没有影响，单独的 1,25(OH)(2)D 仅产生适度的增加。然而，与单独使用 1,25(OH)(2)D 相比，1,25(OH)(2)D 和 PTH 一起协同增加 CYP24 mRNA 水平 3 倍。 PTH 还使 UMR 细胞对 1,25(OH)(2)D 的敏感性从 10(-8) M 增加到 10(-10) M。 PTH 通过 cAMP 信号通路起作用，PTH (3-34) 的作用缺失和 8-溴-cAMP 的全部活性证明了这一点。核连续研究和转染后 CYP24 启动子-报告基因构建体的激活表明，1,25(OH)(2)D 存在下的 PTH 会增加 CYP24 基因转录。 PTH 还增加了 UMR 细胞中维生素 D 受体的数量，但这发生的时间晚于转录的增加。这些研究表明，存在 1,25(OH)(2)D 时，PTH 通过 cAMP 依赖性信号传导途径发挥作用，增加 CYP24 基因的转录，增加 CYP24 蛋白水平，并增加 24-羟化酶活性。
The expression of the vitamin D 24-hydroxylase is highly regulated in target tissues for 1,25-dihydroxyvitamin D-3 (1, 25(OH)(2)D), where it may modulate the action of 1,25(OH)(2)D. In UMR106 osteoblastic cells, 1,25(OH)(2)D and PTH synergistically induce 24-hydroxylase expression. The purpose of these studies was to characterize the interaction between 1,25(OH)(2)D and PTH with regard to the messenger RNA (mRNA) levels of the cytochrome P450 component of the 24-hydroxylase (CYP24). PTH alone had no effect on CYP24 mRNA levels, and 1,25(OH)(2)D alone produced only a modest increase. However, 1,25(OH)(2)D and PTH together synergistically increased CYP24 mRNA levels 3-fold compared with 1,25(OH)(2)D alone. PTH also increased the sensitivity of UMR cells to 1,25(OH)(2)D from 10(-8) to 10(-10) M. PTH worked through the cAMP signaling pathway as evidenced by the lack of effect of PTH (3-34) and by the full activity of 8-bromo-cAMP. PTH in the presence of 1,25(OH)(2)D increased CYP24 gene transcription as shown by nuclear run-on studies and by activation of a CYP24 promoter-reporter construct after transfection. PTH also increased vitamin D receptor number in UMR cells, but this occurred at times later than the increase in transcription. These studies demonstrate that PTH in the presence of 1,25(OH)(2)D works through the cAMP-dependent signaling pathway to increase transcription of the CYP24 gene, to increase CYP24 protein levels, and to increase 24-hydroxylase activity.