Estradiol directly attenuates sodium currents and depolarizing afterpotentials in isolated gonadotropin-releasing hormone neurons.
Estradiol directly attenuates sodium currents and depolarizing afterpotentials in isolated gonadotropin-releasing hormone neurons.
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DOI：
10.1016/j.brainres.2011.12.013
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发表时间：
2012-02-03
期刊：
影响因子：
2.9
通讯作者：
Kuehl-Kovarik MC
中科院分区：
文献类型：
--
作者：
Wang Y;Kuehl-Kovarik MC
促性腺激素释放激素 (GnRH) 神经元是严格调节的生殖轴中的关键控制中心。 GnRH 的释放控制卵巢产生雌二醇，雌二醇作用于下丘脑调节 GnRH 的释放。然而，雌二醇反馈机制才刚刚开始被了解。我们之前已经证明，给予雌性小鼠雌二醇可以调节荧光标记的 GnRH 神经元中的钠电流。在当前的研究中，将雌二醇（1 nM）直接应用于年轻或老年雌性卵巢切除小鼠的下丘脑培养物中，持续 16-24 小时。雌二醇的直接应用调节了年轻和老年动物分离的 GnRH 神经元中的河豚毒素敏感钠电流。雌二醇和特异性雌激素受体-β 激动剂 DPN 降低了早上 (AM) 测量的电流幅度，但对下午电流没有影响。这些化合物还降低了电流响应的上升和衰减斜率，增加了电流宽度，并增加了 AM 记录中的动作电位宽度。此外，雌二醇降低了去极化后电位（DAP）的幅度；这种效应与一天中的时间无关。 ER-β 激动剂 DPN 不能模拟雌二醇对 DAP 的作用，并且雌二醇对 DAP 的调节作用不再存在于生殖后动物的细胞中。这些结果表明，雌二醇可以通过多种途径影响 GnRH 神经元的生理机能，这些途径在向生殖衰老的过渡过程中受到差异性调节，表明雌二醇对 GnRH 神经元输出的调节在衰老过程中受到调节。
The gonadotropin-releasing hormone (GnRH) neuron is the pivotal control center in a tightly regulated reproductive axis. The release of GnRH controls estradiol production by the ovary, and estradiol acts at the hypothalamus to regulate GnRH release. However, the mechanisms of estradiol feedback are just beginning to be understood. We have previously shown that estradiol administered to the female mouse modulates sodium currents in fluorescently-labeled GnRH neurons. In the current studies, estradiol (1 nM) was applied directly, for 16–24 hours, to hypothalamic cultures from young or aged female ovariectomized mice. The direct application of estradiol modulated a tetrodotoxin-sensitive sodium current in isolated GnRH neurons from both young and aged animals. Estradiol, and the specific estrogen receptor-β agonist DPN, decreased current amplitude measured in the morning (AM), but had no effect on afternoon currents. These compounds also decreased the rise and decay slope of the current response, increased the width of the current, and increased action potential width in AM recordings. In addition, estradiol decreased the amplitude of the depolarizing afterpotential (DAP); this effect was not time-of-day dependent. The ER-β agonist DPN did not mimic the effect of estradiol on DAPs, and the modulation of DAPs by estradiol was no longer present in cells from postreproductive animals. These results indicate that estradiol can affect the physiology of GnRH neurons via multiple pathways that are differentially regulated during the transition to reproductive senescence, suggesting that estradiol regulation of GnRH neuronal output is modulated during the aging process.
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影响因子：
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影响因子：
4.8
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