Laboratory of Neuroendocrinology, Department of Neurobiology, David Geffen School of Medicine, Brain Research Institute, University of California Los Angeles, CA, USA.
Front Endocrinol (Lausanne). 2011 Dec 2;2:90. doi: 10.3389/fendo.2011.00090. eCollection 2011.
Our understanding the steroid regulation of neural function has rapidly evolved in the past decades. Not long ago the prevailing thoughts were that peripheral steroid hormones carried information to the brain which passively responded to these steroids. These steroid actions were slow, taking hours to days to be realized because they regulated gene expression. Over the past three decades, discoveries of new steroid receptors, rapid membrane-initiated signaling mechanisms, and de novo neurosteroidogenesis have shed new light on the complexity of steroids actions within the nervous system. Sexual differentiation of the brain during development occurs predominately through timed steroid-mediated expression of proteins and long term epigenetic modifications. In contrast across the estrous cycle, estradiol release from developing ovarian follicles initially increases slowly and then at proestrus increases rapidly. This pattern of estradiol release acts through both classical genomic mechanisms and rapid membrane-initiated signaling in the brain to coordinate reproductive behavior and physiology. This review focuses on recently discovered estrogen receptor-α membrane signaling mechanisms that estradiol utilizes during estrogen positive feedback to stimulate de novo progesterone synthesis within the hypothalamus to trigger the luteinizing hormone (LH) surge important for ovulation and estrous cyclicity. The activation of these signaling pathways appears to be coordinated by the rising and waning of estradiol throughout the estrous cycle and integral to the negative and positive feedback mechanisms of estradiol. This differential responsiveness is part of the timing mechanism triggering the LH surge.
在过去的几十年里，我们对类固醇调节神经功能的理解迅速发展。不久前，流行的观点认为，外周类固醇激素将信息传递到大脑，而大脑被动地对这些类固醇激素做出反应。这些类固醇激素的作用是缓慢的，需要数小时到数天才能实现，因为它们调节基因表达。在过去的三十年中，新的类固醇受体、快速的膜起始信号机制和新的神经甾体生成的发现，为类固醇在神经系统中的作用的复杂性提供了新的认识。大脑在发育过程中的性别分化主要通过定时的类固醇介导的蛋白质表达和长期的表观遗传修饰来实现。相比之下，在发情周期中，来自发育中的卵巢滤泡的雌二醇释放最初缓慢增加，然后在发情前期迅速增加。这种雌二醇释放模式通过经典的基因组机制和大脑中的快速膜起始信号来协调生殖行为和生理学。这篇综述重点介绍了最近发现的雌激素受体-α膜信号机制，雌二醇利用这些机制在雌激素正反馈中刺激新合成的孕激素在下丘脑内的合成，从而触发黄体生成素 (LH) 激增，这对排卵和发情周期的周期性很重要。这些信号通路的激活似乎是由发情周期中雌二醇的上升和下降协调的，并且是雌二醇负反馈和正反馈机制的组成部分。这种差异反应是触发 LH 激增的定时机制的一部分。
