The influence of estradiol on nervous system function.
The influence of estradiol on nervous system function.
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DOI：
10.1358/dnp.2005.18.10.959578
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发表时间：
2005-12
影响因子：
--
通讯作者：
Marissa I. Boulware;P. Mermelstein
中科院分区：
文献类型：
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作者：
Marissa I. Boulware;P. Mermelstein
在神经系统中，雌二醇最初的特征是其在性成熟和生殖中的关键作用。然而，现已确定雌二醇影响多种大脑功能，包括学习和记忆、精细运动控制、疼痛感知和情绪。与范围扩大的同时，雌二醇作用的新机制也正在被阐明。传统上，雌二醇通过细胞内雌激素受体（ERα和ERβ，它们通过与雌激素反应元件（ERE）结合来调节转录而发挥作用。这些功能对性行为至关重要，被称为“基因组”，与“非基因组”效应不同，“非基因组”效应是雌二醇通过膜表面启动的过程产生神经元功能快速变化的结果。最近的进展表明，这些功能对性行为至关重要。 非基因组效应也由位于质膜的经典雌激素受体介导。此外，雌二醇刺激膜表面的雌激素受体会激活 G 蛋白偶联受体 (GPCR) 信号传导，从而导致神经元兴奋性的短期和长期变化。相关的是，大脑本身合成雌激素，允许类固醇发出局部信号， 对性腺分泌的依赖性较小。这篇综述概述了雌激素作用的既定和最新发现的要点，这些不同的机制如何协同作用来调节神经系统功能，并概述了关于雌激素在大脑中的影响仍然存在的几个问题。
Within the nervous system, estradiol was originally characterized through its critical role in sexual maturation and reproduction. However, it is now firmly established that estradiol affects a diverse array of brain functions including learning and memory, fine motor control, pain perception and mood. In parallel with this increased scope, new mechanisms of estradiol action are being elucidated. Traditionally, estradiol was known to work through intracellular estrogen receptors (ERalpha and ERbeta, which regulate transcription by binding to estrogen response elements (EREs). These functions, critical for sexual behavior, are termed "genomic" and are distinct from "nongenomic" effects whereby estradiol produces rapid changes in neuronal function by processes initiated at the membrane surface. Recent advances have demonstrated that these nongenomic effects are also mediated by classical estrogen receptors that are localized to the plasma membrane. Further, stimulation of estrogen receptors on the membrane surface by estradiol activates G-protein-coupled receptor (GPCR) signaling, which can lead to both short- and long-term changes in neuronal excitability. Related, the brain itself synthesizes estrogens, allowing for localized signaling by the steroid that is less dependent on gonadal secretion. This review outlines highlights from both established and recent findings of estrogen action, how these diverse mechanisms act in concert to regulate nervous system function, and outlines several questions that still remain regarding the effects of estrogen in brain.