Early growth response protein 1 binds to the luteinizing hormone-beta promoter and mediates gonadotropin-releasing hormone-stimulated gene expression.
Early growth response protein 1 binds to the luteinizing hormone-beta promoter and mediates gonadotropin-releasing hormone-stimulated gene expression.
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DOI：
10.1210/mend.13.5.0276
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发表时间：
1999-05
影响因子：
--
通讯作者：
M. W. Wolfe;G. B. Call
中科院分区：
文献类型：
--
作者：
M. W. Wolfe;G. B. Call
下丘脑神经肽 GnRH 调节垂体促性腺激素的 LH 合成和分泌。此外，体外和体内研究表明，LH β 亚基基因受转录因子类固醇生成因子-1 (SF-1) 和早期生长反应蛋白 1 (Egr1) 的调节。本研究调查了 Egr1 和 SF-1 在调节促性腺激素细胞系 α T3-1 中马 LH β 亚基启动子活性中所起的作用，以及这些因子和顺式作用元件在 GnRH 调节启动子中的重要性。发现 Egr 家族的所有四个成员都能诱导马启动子的活性。负责 Egr 诱导的区域位于启动子的近端 185 bp，其中包含两个 Egr 响应元件。 Egr1 和 SF-1 的共表达导致马 (e)LH beta 启动子的协同激活。任何 Egr 或 SF-1 反应元件的突变都会减弱这种协同作用。 α T3-1 细胞中 Egr1 的内源表达在基础条件下检测不到，但在 GnRH 刺激后迅速被诱导。对含有突变 Egr 或 SF-1 位点的启动子构建体的重新检查表明，这些位点是 GnRH 诱导所必需的。事实上，eLH β 启动子内两个 Egr 位点的突变完全减弱了 GnRH 对其的诱导作用。因此，GnRH 诱导 Egr1 表达，随后激活 eLH β 启动子。最后，GnRH 不仅诱导 Egr1 的表达，还诱导其辅阻遏物 NGFI-A (Egr1) 结合蛋白 (Nab1)，它可以抑制 Egr1 诱导的 eLH β 启动子的转录。
The hypothalamic neuropeptide, GnRH, regulates the synthesis and secretion of LH from pituitary gonadotropes. Furthermore, it has been shown that the LH beta-subunit gene is regulated by the transcription factors steroidogenic factor-1 (SF-1) and early growth response protein 1 (Egr1) in vitro and in vivo. The present study investigated the roles played by Egr1 and SF-1 in regulating activity of the equine LH beta-subunit promoter in the gonadotrope cell line, alpha T3-1, and the importance of these factors and cis-acting elements in regulation of the promoter by GnRH. All four members of the Egr family were found to induce activity of the equine promoter. The region responsible for induction by Egr was localized to the proximal 185 bp of the promoter, which contained two Egr response elements. Coexpression of Egr1 and SF-1 led to a synergistic activation of the equine (e)LH beta promoter. Mutation of any of the Egr or SF-1 response elements attenuated this synergism. Endogenous expression of Egr1 in alpha T3-1 cells was not detectable under basal conditions, but was rapidly induced after GnRH stimulation. Reexamination of the promoter constructs harboring mutant Egr or SF-1 sites indicated that these sites were required for GnRH induction. In fact, mutation of both Egr sites within the eLH beta promoter completely attenuated its induction by GnRH. Thus, GnRH induces expression of Egr1, which subsequently activates the eLH beta promoter. Finally, GnRH not only induced expression of Egr1, but also its corepressor, NGFI-A (Egr1) binding protein (Nab1), which can repress Egr1- induced transcription of the eLH beta promoter.