Shupnik M A
Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA 22908, USA.
J Neuroendocrinol. 2002 Feb;14(2):85-94. doi: 10.1046/j.0007-1331.2001.00744.x.
Information on oestrogen action has grown exponentially in the past decade, and recent studies have begun to define the mechanism of ligand-dependent activation and cell-specific effects. Oestrogen-mediated gene transcription in a specific tissue depends on several factors, the most important of which is the presence of at least one of the two nuclear oestrogen receptor (ER) isoforms, ER(alpha) and ERbeta. The presence and levels of specific ER isoform variants, along with receptor coactivator, corepressor and integrator proteins, directly modulate overall nuclear ER activity. The structure of the ligand, including both physiological oestrogens and synthetic oestrogen receptor modulators, influences ER interactions with these other proteins and thus determines the biological response. Furthermore, peptide and neurotransmitter-stimulated intracellular signalling pathways activate specific enzyme cascades and may modify the receptors and their interacting proteins, resulting in either independent or ligand-enhanced ER-mediated responses. Finally, several rapid effects of oestrogen probably occur at the membrane through nongenomic pathways that may or may not require the same ER proteins that are found in the nucleus. This review concentrates on the pituitary-hypothalamic axis and the genomic effects of oestrogen, and discusses the current knowledge of each of these factors in determining oestrogen actions in the neuroendocrine system.
在过去十年间，关于雌激素作用的信息呈指数级增长，近期研究已开始明确配体依赖性激活机制及细胞特异性效应。雌激素介导的特定组织中的基因转录取决于多个因素，其中最重要的是两种核雌激素受体（ER）亚型ERα和ERβ中至少有一种的存在。特定ER亚型变体的存在及水平，连同受体共激活因子、共抑制因子和整合蛋白，直接调节整体核ER活性。配体的结构，包括生理性雌激素和合成雌激素受体调节剂，影响ER与这些其他蛋白的相互作用，从而决定生物学反应。此外，肽和神经递质刺激的细胞内信号通路激活特定的酶级联反应，并可能改变受体及其相互作用蛋白，导致独立的或配体增强的ER介导反应。最后，雌激素的几种快速效应可能通过非基因组途径在细胞膜发生，这些途径可能需要也可能不需要与细胞核中相同的ER蛋白。本综述聚焦于垂体 - 下丘脑轴及雌激素的基因组效应，并讨论了这些因素在决定雌激素在神经内分泌系统中的作用方面的现有知识。
