Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity
Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity
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DOI：
10.1073/pnas.0504270102
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发表时间：
2005-10-25
影响因子：
11.1
通讯作者：
Moenter, SM
中科院分区：
文献类型：
--
作者：
Christian, CA;Mobley, JL;Moenter, SM
一个强大的促性腺激素释放激素（GnRH）激增是促黄体生成激素（LH）激增触发排卵的先决条件。在啮齿类动物中，促性腺激素释放激素激增是由雌二醇升高和雌激素作用从负反馈到正反馈的昼夜转换引发的。在卵巢切除（OVX）或OVX并用雌二醇植入物（OVX+E）治疗的成年小鼠中检测了恒定雌二醇治疗诱导每日LH峰的能力。OVX小鼠的LH无时间差异。相比之下，OVX+E小鼠表现出较大的LH激增（相对于上午8至124倍）。在OVX +E后第2-5天的下午样品中。靶向细胞外记录用于检查脑切片中GnRH神经元放电活动的变化。在OVX小鼠的细胞中没有时间差异。相反，与上午记录的细胞相比，在下午记录的OVX+E细胞显示出增加的平均放电率和瞬时放电频率，这可以增加GnRH释放，并减少放电发作之间的静止持续时间，可能反映了增加的脉冲频率。与OVX细胞相比，OVX+E细胞显示反映负反馈的GnRH神经元放电的变化，而在p.m.，OVX+E细胞表现出正反馈的变化。这些数据表明，不同的模式和水平的个别GnRH神经元放电可能反映了开关雌二醇的行动和基础GnRH浪涌的产生。切片中GnRH神经元活性改变的持续性表明这种方法可用于研究浪涌产生的神经生物学机制。
A robust gonadotropin-releasing hormone (GnRH) surge is a prerequisite signal for the luteinizing hormone (LH) surge that triggers ovulation. in rodents, the GnRH surge is initiated by elevated estradiol and a diurnal switch in estrogen action from negative to positive feedback. The ability of constant estradiol treatment to induce daily LH surges was tested in adult mice that were ovariectomized (OVX) or OVX and treated with estradiol implants (OVX+E). LH in OVX mice showed no time-of-day difference. in contrast, OVX+E mice showed a large LH surge (8- to 124-fold relative to the a.m.) in p.m. samples on d 2-5 post-OVX+E. Targeted extracellular recordings were used to examine changes in firing activity of GnRH neurons in brain slices. There was no time-of-day difference in cells from OVX mice. In contrast, OVX+E cells recorded in the p.m. showed an increased mean firing rate and instantaneous firing frequency, which could increase GnRH release, and decreased duration of quiescence between bouts of firing, possibly reflecting increased pulse frequency, compared with cells recorded in the a.m. In the a.m., OVX+E cells showed changes in GnRH neuron firing reflecting negative feedback compared with OVX cells, whereas in the p.m., OVX+E cells exhibited changes suggesting positive feedback. These data indicate that differences in pattern and level of individual GnRH neuron firing may reflect the switch in estradiol action and underlie GnRH surge generation. The persistence of altered GnRH neuron activity in slices indicates that this approach can be used to study the neurobiological mechanisms of surge generation.