Membrane estrogen receptor-α interactions with metabotropic glutamate receptor 1a modulate female sexual receptivity in rats
Membrane estrogen receptor-α interactions with metabotropic glutamate receptor 1a modulate female sexual receptivity in rats
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DOI：
10.1523/jneurosci.0592-07.2007
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发表时间：
2007-08-29
影响因子：
5.3
通讯作者：
Micevych, Paul
中科院分区：
文献类型：
--
作者：
Dewing, Phoebe;Boulware, Marissa I.;Micevych, Paul
在大鼠中，雌性性行为是由一个明确的边缘-下丘脑回路来调节的，该回路整合了感觉和激素信息。该回路的兴奋激活导致内侧视前核中的μ阿片受体（莫尔）内化，这是性感受性充分表达的重要步骤。雌二醇通过膜和细胞内受体影响神经元的活动和行为，但雌二醇介导的膜反应在体内的机制和生理意义仍然是难以捉摸的。最近的体外证据发现，膜相关雌激素受体α（ER α）的刺激导致代谢型谷氨酸受体1a（mGluR 1a）的激活。此外，mGluR 1a信号是负责观察到的雌二醇的下游效应。在这里，我们提出的数据表明，ER α和mGluR 1a直接相互作用，以介导快速雌二醇诱导的激活莫尔在内侧视前核，导致女性的性感受性。此外，阻断下丘脑弓状核中的mGluR 1a导致雌二醇诱导的莫尔内化显著减弱，导致女性性行为减少。这些结果将膜启动的雌二醇作用与调节行为的神经事件联系起来，证明了ER α至mGluR 1a信号传导的生理重要性。
In rats, female sexual behavior is regulated by a well defined limbic-hypothalamic circuit that integrates sensory and hormonal information. Estradiol activation of this circuit results in mu-opioid receptor (MOR) internalization in the medial preoptic nucleus, an important step for full expression of sexual receptivity. Estradiol acts through both membrane and intracellular receptors to influence neuronal activity and behavior, yet the mechanism(s) and physiological significance of estradiol-mediated membrane responses in vivo have remained elusive. Recent in vitro evidence found that stimulation of membrane-associated estrogen receptor-alpha(ER alpha) led to activation of metabotropic glutamate receptor 1a ( mGluR1a). Furthermore, mGluR1a signaling was responsible for the observed downstream effects of estradiol. Here we present data that show that ER alpha and mGluR1a directly interact to mediate a rapid estradiol-induced activation of MOR in the medial preoptic nucleus, leading to female sexual receptivity. In addition, blockade of mGluR1a in the arcuate nucleus of the hypothalamus resulted in a significant attenuation of estradiol-induced MOR internalization, leading to diminished female sexual behavior. These results link membrane-initiated estradiol actions to neural events modulating behavior, demonstrating the physiological importance of ER alpha-to-mGluR1a signaling.