Epidermal growth factor receptor kinase activity is required for gap junction closure and for part of the decrease in ovarian follicle cGMP in response to LH.
Epidermal growth factor receptor kinase activity is required for gap junction closure and for part of the decrease in ovarian follicle cGMP in response to LH.
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DOI：
10.1530/rep-10-0288
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Jaffe LA
中科院分区：
文献类型：
--
作者：
Norris RP;Freudzon M;Nikolaev VO;Jaffe LA
小鼠卵母细胞减数分裂细胞周期被阻滞在前期，然后当促黄体生成素（LH）作用于周围的颗粒细胞时，减数分裂细胞周期重新启动。颗粒细胞通过提供cGMP的来源来阻止减数分裂，cGMP通过间隙连接扩散到卵母细胞中，LH通过关闭连接和减少颗粒细胞cGMP来重新启动细胞周期，从而降低卵母细胞cGMP。表皮生长因子受体（EGFR）激活是触发LH诱导的减数分裂恢复的重要步骤，但其与卵泡中cGMP减少的关系尚不完全清楚，其在导致间隙连接闭合中的可能功能尚未研究。在这里，我们使用EGFR激动剂（epiregulin和amphiregulin），和EGFR激酶抑制剂（AG1478），以研究EGFR在导致卵母细胞从前期停滞释放的信号通路中的功能。我们的研究结果表明，EGFR激酶有助于LH诱导的减数分裂恢复在两个不同的方式。首先，它是缝隙连接闭合所必需的。其次，它是卵泡cGMP减少的重要组成部分。我们的数据表明，EGFR激酶依赖的cGMP减少的组成部分是LH诱导的减数分裂恢复所需的，但他们也表明，一个尚未确定的途径占cGMP减少的很大一部分。
The meiotic cell cycle in mouse oocytes is arrested in prophase, and then restarted when luteinizing hormone (LH) acts on the surrounding granulosa cells. The granulosa cells keep meiosis arrested by providing a source of cGMP that diffuses into the oocyte through gap junctions, and LH restarts the cell cycle by closing the junctions and by decreasing granulosa cell cGMP, thus lowering oocyte cGMP. Epidermal growth factor receptor (EGFR) activation is an essential step in triggering LH-induced meiotic resumption, but its relationship to the cGMP decrease in the follicle is incompletely understood, and its possible function in causing gap junction closure has not been investigated. Here we use EGFR agonists (epiregulin and amphiregulin), and an EGFR kinase inhibitor (AG1478) to study the function of the EGFR in the signaling pathways leading to the release of oocytes from prophase arrest. Our results indicate that the EGFR kinase contributes to LH-induced meiotic resumption in two different ways. First, it is required for gap junction closure. Second, it is required for an essential component of the decrease in follicle cGMP. Our data show that the EGFR kinase-dependent component of the cGMP decrease is required for LH-induced meiotic resumption, but they also indicate that an as yet unidentified pathway accounts for a large part of the cGMP decrease.