Advances in understanding corticotrophin-releasing hormone gene expression
Advances in understanding corticotrophin-releasing hormone gene expression
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DOI：
10.2741/2084
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Nicholson, Richard C.
中科院分区：
文献类型：
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作者：
King, Bruce R.;Nicholson, Richard C.
糖皮质激素抑制下丘脑室旁核（PVN）中促肾上腺皮质激素释放激素（CRH）基因的表达，但刺激胎盘中的表达。在AtT20细胞（PVN CRH产生的模型）中，cAMP产生高水平的启动子活性。循环AMP刺激通过cAMP反应元件（CRE）和尾侧型同源盒蛋白反应元件（CDXARE）发生。CRE是cAMP反应单元的一部分，cAMP反应单元包括混合类固醇反应元件（HRE）、皮质激素反应元件（EcRE）、金属反应转录因子-1反应元件（MTFRE）、阴阳1反应元件（YY1RE）和糖皮质激素负反应元件（nGRE）。环AMP作用于HRE、EcRE和MTFRE，阻断YY1RE介导的CRE抑制。作用于nGRE的糖皮质激素抑制CRE的cAMP激活。在胎盘细胞中，CRH启动子具有较低的内在基础活性，cAMP导致其活性适度增加。糖皮质激素和cAMP的刺激以及雌激素和雌激素受体α的抑制通过CRE发生。在AtT20细胞中，多个反应元件协调对cAMP和糖皮质激素的反应，而在胎盘细胞中，CRE是单独起作用的。这些启动子功能的差异导致满足特定生理需求的反应。
Glucocorticoids inhibit corticotrophin-releasing hormone (CRH) gene expression in the hypothalamic paraventricular nucleus (PVN), but stimulate expression in the placenta. In AtT20 cells ( a model of PVN CRH production) cAMP produces a high level of promoter activity. Cyclic AMP stimulation occurs through the cAMP response element (CRE) and the caudal type homeobox protein response element (CDXARE). The CRE acts as part of a cAMP response unit that includes the hybrid steroid response element (HRE), ecdysone response element (EcRE), metal-responsive transcription factor-1 response element (MTFRE), ying yang 1 response element (YY1RE) and negative glucocorticoid response element (nGRE). Cyclic AMP acts on the HRE, EcRE and MTFRE to block YY1RE mediated inhibition of the CRE. Glucocorticoids acting at the nGRE inhibit cAMP activation of the CRE. In placental cells the CRH promoter has low intrinsic basal activity and cAMP causes a modest increase in activity. Stimulation by glucocorticoids and cAMP and inhibition by estrogen and estrogen receptor alpha occurs through the CRE. In AtT20 cells multiple response elements coordinate a response to cAMP and glucocorticoids while in placental cells the CRE acts in isolation. These differences in promoter function lead to responses that meet specific physiological needs.