Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles.
Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles.
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DOI：
10.1530/rep-08-0457
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发表时间：
2009-05
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影响因子：
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通讯作者：
Christenson LK
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文献类型：
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作者：
Carletti MZ;Christenson LK
促黄体生成激素（LH）通过激活PKA通路以及其他细胞信号传导级联来作用于排卵期颗粒细胞，以增加排卵和黄体化所必需的特定基因的转录。总的来说，这些细胞信号传导反应发生迅速（在几分钟内），然而，目前没有高通量研究报告LH激增后4小时前的变化。为了鉴定可能对排卵和黄体化的启动至关重要的早期反应基因，在hCG之前和之后1小时收集小鼠颗粒细胞。57个基因转录本在hCG后显著上调（p<0.05），3个下调。已知这些转录本中有24种在LH/hCG高峰后的较晚时间点表达，而36种未知由排卵期颗粒细胞表达。通过定量RT-PCR分析了几种转录物的时间表达，包括转录因子Nr 4a 1，Nr 4a 2，Egr 1，Egr 2，Btg 1和Btg 2，以及EGF样配体Areg和Ereg，并讨论了它们在颗粒细胞功能中的假定作用。Epigen（Epgn）是EGF样配体家族的另一个成员，首次在颗粒细胞中被LH/hCG快速诱导。我们证明Epgn启动卵丘扩张，类似于其他EGF受体配体Areg和Ereg。这些研究表明，在体内的基因表达的变化发生在LH的反应，许多差异表达的基因是转录因子，我们预测反过来调节颗粒细胞基因表达，最终影响排卵和黄体化的过程。
Luteinizing hormone (LH) acts on periovulatory granulosa cells by activating the PKA pathway as well as other cell signaling cascades to increase the transcription of specific genes necessary for ovulation and luteinization. Collectively, these cell signaling responses occur rapidly (within minutes), however, presently no high throughput studies have reported changes before 4 h after the LH surge. To identify early response genes that are likely critical for initiation of ovulation and luteinization, mouse granulosa cells were collected before and 1 h after hCG. Fifty-seven gene transcripts were significantly (p<0.05) upregulated and 3 downregulated following hCG. Twenty-four of these transcripts were known to be expressed after the LH/hCG surge at later time points, while 36 were unknown to be expressed by periovulatory granulosa cells. Temporal expression of several transcripts, including the transcription factors Nr4a1, Nr4a2, Egr1, Egr2, Btg1, and Btg2, and the EGF-like ligands Areg and Ereg, were analyzed by quantitative RT-PCR, and their putative roles in granulosa cell function are discussed. Epigen (Epgn), another member of the family of EGF-like ligands, was identified for the first time in granulosa cells as rapidly induced by LH/hCG. We demonstrate that Epgn initiates cumulus expansion, similar to the other EGF-receptor ligands Areg and Ereg. These studies illustrate that a number of changes in gene expression occur in vivo in response to LH, and that many of the differentially expressed genes are transcription factors that we would predict in turn modulate granulosa cell gene expression to ultimately impact the processes of ovulation and luteinization.