PROSTAGLANDIN E2 MODULATES PRESYNAPTIC REGULATION OF GNRH NEURONS VIA EP4 RECEPTORS IN ACCORDANCE WITH ESTROGEN MILIEU
PROSTAGLANDIN E2 MODULATES PRESYNAPTIC REGULATION OF GNRH NEURONS VIA EP4 RECEPTORS IN ACCORDANCE WITH ESTROGEN MILIEU
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DOI：
10.1016/j.neuroscience.2017.07.025
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发表时间：
2017-09-30
期刊：
影响因子：
3.3
通讯作者：
Akema, Tatsuo
中科院分区：
文献类型：
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作者：
Fujioka, Hitomi;Funabashi, Toshiya;Akema, Tatsuo
前列腺素E2（PGE 2）通过调节下丘脑中释放促性腺激素释放激素（GnRH）的神经元的活性来促进促性腺激素分泌。然而，PGE 2在这些神经元中的作用机制尚未完全探索。我们研究了PGE 2对GnRH神经元产生微型兴奋性突触后电流（mEPSC）的影响，通过全细胞膜片钳记录进行测量。在从雌性GnRH-EGFP大鼠的视前区制备的切片中鉴定GnRH神经元。暴露于PGE 2显着增加的频率，但不是振幅，产生的mEPSCs的发情前期的一天，但既不改变频率也不改变振幅的间情期的第1天。这些数据表明，前列腺素E2对mEPSC频率的作用取决于发情阶段。PGE 2作用的雌激素依赖性进一步得到了增加的频率的支持，但不是振幅，mEPSC产生于从雌激素引发的卵巢切除大鼠制备的GnRH神经元。相反，在胆固醇处理的大鼠中，PGE 2对GnRH神经元的mEPSC频率或振幅没有影响。随后鉴定PG 2 E作用的候选受体的实验显示，暴露于PGE 2受体4（EP 4）激动剂，而不是EP 1或EP 2激动剂，模拟了PGE 2暴露所实现的效果。使用EP 4拮抗剂可以逆转mEPSC的这些作用，说明了该作用的特异性。总的来说，这些数据表明，PGE 2可以改变兴奋性突触神经传递的GnRH神经元通过EP 4信号在突触前位点（S）在动情前期雌激素依赖的方式。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Prostaglandin E2 (PGE2) promotes gonadotropin secretion by regulating the activity of neurons that release gonadotropin-releasing hormone (GnRH) in the hypothalamus. However, the mechanisms of action of PGE2 at these neurons have yet to be fully explored. We examined the effects of PGE2 on the generation of miniature excitatory postsynaptic currents (mEPSCs) at GnRH neurons as measured by whole-cell, patch-clamp recordings. GnRH neurons were identified in slices prepared from the preoptic areas of female GnRH-EGFP rats. Exposure to PGE2 significantly increased the frequency, but not the amplitude, of the mEPSCs generated on the day of proestrus, but neither frequency nor amplitude was altered on day 1 of diestrus. These data suggest that the action of PGE2 on mEPSC frequency varies depending on the stage of estrous. An estrogen-dependence of PGE2's action was further supported by the increased frequency, but not amplitude, of mEPSCs generated at GnRH neurons prepared from estrogen-primed ovariectomized rats. Conversely, PGE2 had no effect on mEPSC frequency or amplitude at GnRH neurons in cholesterol-treated rats. Subsequent experiments to identify candidate receptors for PG2E's action revealed that exposure to a PGE2 receptor 4 (EP4) agonist, but not EP1 or EP2 agonists, mimicked the effects achieved by PGE2 exposure. These effects of mEPSCs could be reversed using an EP4 antagonist, illustrating the specificity of the effect. Collectively, these data demonstrate that PGE2 can alter excitatory synaptic neurotransmission at GnRH neurons via EP4 signaling at presynaptic site(s) in an estrogen-dependent fashion during proestrus. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.