van Leeuwen J P, Birkenhäger J C, Vink-van Wijngaarden T, van den Bemd G J, Pols H A
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Biochem Biophys Res Commun. 1992 Jun 30;185(3):881-6. doi: 10.1016/0006-291x(92)91709-y.
We studied the effect of parathyroid hormone (PTH) and activation of the cAMP signal pathway on vitamin D receptor (VDR) mRNA levels in the phenotypically osteoblast cell line UMR 106. PTH caused a time- and dose-dependent increase of the VDR mRNA content with a maximum after 2 h. After 24 h the VDR mRNA level in PTH-treated cells returned to control level. In contrast, the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced increase in VDR mRNA did not decline after 24 h. Inhibition of transcription with actinomycin D (10 micrograms/ml) completely abolished the PTH-induced increase of VDR mRNA and inhibition of translation with cycloheximide (1 microgram/ml) resulted in superinduction of VDR mRNA. The role of cAMP in the induction of VDR mRNA was studied with several agents acting via the cAMP pathway. Incubation for 2 and 4 h with forskolin, Bt2cAMP, PTHrP or prostaglandin E2 caused an increase in the level of VDR mRNA comparable to that caused by PTH. The calcium ionophore A23187 did not affect VDR mRNA level. The present study demonstrates that PTH and activation of the cAMP signal pathway cause up-regulation of VDR via induction of VDR gene expression. The effect of cAMP on the VDR gene is suggestive for a cAMP responsive element in the VDR gene.
我们研究了甲状旁腺激素（PTH）及环磷酸腺苷（cAMP）信号通路激活对成骨细胞表型的UMR 106细胞系中维生素D受体（VDR）mRNA水平的影响。PTH导致VDR mRNA含量呈时间和剂量依赖性增加，2小时后达到最大值。24小时后，经PTH处理的细胞中VDR mRNA水平恢复至对照水平。相比之下，1,25 - 二羟维生素D3（1,25(OH)2D3）诱导的VDR mRNA增加在24小时后并未下降。用放线菌素D（10微克/毫升）抑制转录完全消除了PTH诱导的VDR mRNA增加，用环己酰亚胺（1微克/毫升）抑制翻译导致VDR mRNA超诱导。利用几种通过cAMP途径起作用的试剂研究了cAMP在诱导VDR mRNA中的作用。用福斯高林、Bt2cAMP、甲状旁腺激素相关蛋白（PTHrP）或前列腺素E2孵育2小时和4小时导致VDR mRNA水平升高，与PTH引起的升高相当。钙离子载体A23187不影响VDR mRNA水平。本研究表明，PTH及cAMP信号通路激活通过诱导VDR基因表达导致VDR上调。cAMP对VDR基因的作用提示VDR基因中存在一个cAMP反应元件。
