Vasoactive intestinal polypeptide can excite gonadotropin-releasing hormone neurons in a manner dependent on estradiol and gated by time of day
Vasoactive intestinal polypeptide can excite gonadotropin-releasing hormone neurons in a manner dependent on estradiol and gated by time of day
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DOI：
10.1210/en.2007-1098
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发表时间：
2008-06-01
期刊：
影响因子：
4.8
通讯作者：
Moenter, Suzanne M.
中科院分区：
文献类型：
--
作者：
Christian, Catherine A.;Moenter, Suzanne M.
促性腺激素释放激素释放的激增信号LH激增，触发排卵。GnRH激增依赖于雌二醇反馈从阴性到阳性的转换，在啮齿动物中，依赖于日常神经信号，可能来自视交叉上核。血管活性肠肽（VIP）可能参与视交叉上核-GnRH神经元的通讯。在这里，我们评估了急性VIP（5分钟治疗）对GnRH神经元功能的影响，使用脑切片中GnRH神经元放电活动的靶向细胞外记录。我们研究了VIP在一天中不同时间对放电率的影响，使用已建立的卵巢切除，雌二醇治疗（OVX+E）小鼠模型，该模型显示每日LH峰定时到下午晚些时候。来自OVX动物（无雌二醇）的细胞对VIP没有反应，无论一天中的什么时间。在雌二醇作用下，VIP对GnRH神经元的作用呈时间依赖性。在负反馈过程中，OVX+E细胞没有反应。VIP增加记录在浪涌发作期间的细胞中的放电，但这种兴奋性反应在浪涌峰值时减少。在峰期用VIP受体拮抗剂急性处理OVX+E细胞可减少GnRH神经元放电。这表明内源性VIP可能在浪涌期间增加GnRH神经元放电并阻断对外源性VIP的反应。这些数据为VIP对GnRH神经元的作用提供了功能证据，并表明雌二醇和一天中的时间门控GnRH神经元对该肽的反应。VIP可以提供来自生物钟的兴奋信号，帮助确定GnRH激增的时间。
A surge of GnRH release signals the LH surge that triggers ovulation. The GnRH surge is dependent on a switch in estradiol feedback from negative to positive and, in rodents, a daily neural signal, likely from the suprachiasmatic nuclei. Vasoactive intestinal polypeptide (VIP) may be involved in suprachiasmatic nuclei-GnRH neuron communication. Here we assessed the effects of acute VIP (5 min treatment) on GnRH neuron function using targeted extracellular recordings of firing activity of GnRH neurons in brain slices. We examined the effect of VIP on firing rate at different times of day using an established ovariectomized, estradiol-treated (OVX+E) mouse model that exhibits daily LH surges timed to the late afternoon. Cells from OVX animals (no estradiol) did not respond to VIP, regardless of time of day. With estradiol, the effect of VIP on GnRH neurons was dependent on the time of recording. During negative feedback, OVX+E cells did not respond. VIP increased firing in cells recorded during surge onset, but this excitatory response was reduced at surge peak. Acute treatment of OVX+E cells during surge peak with a VIP receptor antagonist decreased GnRH neuron firing. This suggests endogenous VIP may both increase GnRH neuron firing during the surge and occlude response to exogenous VIP. These data provide functional evidence for VIP effects on GnRH neurons and indicate that both estradiol and time of day gate the GnRH neuron response to this peptide. VIP may provide an excitatory signal from the circadian clock that helps time the GnRH surge.