Estradiol induces diurnal shifts in GABA transmission to gonadotropin-releasing hormone neurons to provide a neural signal for ovulation
Estradiol induces diurnal shifts in GABA transmission to gonadotropin-releasing hormone neurons to provide a neural signal for ovulation
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DOI：
10.1523/jneurosci.4738-06.2007
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发表时间：
2007-02-21
影响因子：
5.3
通讯作者：
Moenter, Suzanne M.
中科院分区：
文献类型：
--
作者：
Christian, Catherine A.;Moenter, Suzanne M.
排卵是由大脑分泌促性腺激素释放激素（GnRH）的激增启动的。GnRH通常受卵巢类固醇的负反馈控制。然而，在生殖周期的卵泡晚期持续暴露于雌二醇期间，这种类固醇的反馈作用转为阳性，诱导激增。在这里，我们使用了一个已建立的卵巢切除，雌二醇治疗（OVX + E）小鼠模型，表现出每日浪涌调查这种开关背后的神经生物学机制。具体来说，我们研究了GABA传递到GnRH神经元的变化，这可以通过GABA（A）受体激活来兴奋。在OVX + E和OVX小鼠GnRH神经元的冠状和矢状切片上记录自发GABA能突触后电流（PSC）。在任一切片方向上，OVX小鼠细胞中PSC频率均无昼夜变化。在OVX + E细胞在两个方向，PSC频率低，负反馈期间，但在浪涌发作增加。在浪涌峰值期间，这种增加在冠状切片中消退，但在矢状切片中持续存在。比较河豚毒素（TTX）处理前和处理期间的PSC显示，TTX降低了OVX + E细胞中矢状切片的PSC频率，但冠状切片没有。这表明雌二醇作用于多种GABA能传入群体，通过活动依赖性和非依赖性机制增加传递。在浪涌期间，Ehrs也增加了PSC幅度。因此，兴奋和昼夜周期相互作用，以诱导GABA传递和突触后反应的变化，这将产生适当的GnRH神经元放电活动和激素释放的变化。
Ovulation is initiated by a surge of gonadotropin-releasing hormone (GnRH) secretion by the brain. GnRH is normally under negative feedback control by ovarian steroids. During sustained exposure to estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of this steroid switches to positive, inducing the surge. Here, we used an established ovariectomized, estradiol-treated (OVX + E) mouse model exhibiting daily surges to investigate the neurobiological mechanisms underlying this switch. Specifically, we examined changes in GABA transmission to GnRH neurons, which can be excited by GABA(A) receptor activation. Spontaneous GABAergic postsynaptic currents (PSCs) were recorded in GnRH neurons from OVX + E and OVX mice in coronal and sagittal slices. There were no diurnal changes in PSC frequency in cells from OVX mice in either slice orientation. In OVX + E cells in both orientations, PSC frequency was low during negative feedback but increased at surge onset. During the surge peak, this increase subsided in coronal slices but persisted in sagittal slices. Comparison of PSCs before and during tetrodotoxin (TTX) treatment showed TTX decreased PSC frequency in OVX + E cells in sagittal slices, but not coronal slices. This indicates estradiol acts on multiple GABAergic afferent populations to increase transmission through both activity-dependent and -independent mechanisms. Estradiol also increased PSC amplitude during the surge. Estradiol and the diurnal cycle thus interact to induce shifts in both GABA transmission and postsynaptic response that would produce appropriate changes in GnRH neuron firing activity and hormone release.