EAGER: Cloning of a CNS Membrane Estrogen Receptor

雌激素是类固醇激素，几乎影响身体的每一个组织，包括大脑。 雌激素的所有作用都归因于它与雌激素受体的结合。古典音乐？细胞内雌激素受体ER α和ER β以及随后的基因激活，这是一个缓慢的事件。 然而，有压倒性的生理学证据表明，雌激素在大脑和其他非神经组织中具有快速作用，这些组织不涉及这些经典受体，而是被认为涉及质膜定位的雌激素受体。事实上，已经合成了一种称为STX的新型化合物，它选择性地激活这种膜雌激素受体，并介导许多归因于雌激素的生理过程，而没有促进生长的作用。 膜雌激素受体的结构尚不清楚，虽然其细胞信号传导特性的方面已经阐明。因此，本项目的目的是确定和克隆膜雌激素受体使用完善的功能克隆策略。我们的两位神经科学研究生将在大脑和非神经组织中鉴定表达膜雌激素受体的特定位点。膜雌激素受体的鉴定将为研究雌激素生物学开辟新的天地并产生新的方法，特别是在女性的低雌激素状态下变得失调的生理功能（能量和骨稳态、温度调节、应激反应、昼夜节律、睡眠周期、学习/记忆和情绪）（例如，绝经期）。此外，世界各地的学生和研究员已经利用STX来探测多种组织（脑、骨、肝和胰腺）中膜雌激素受体的功能，并且将从具有膜雌激素受体克隆中受益匪浅，因为克隆的雌激素受体的基因序列将立即存放在GeneBank中以供更广泛的研究团体使用。因此，克隆膜雌激素受体不仅对神经科学家，而且对全世界生命科学的学生都有巨大的好处。

Estrogens are steroid hormones that affect virtually every tissue in the body including the brain. All of the actions of estrogen have been ascribed to its binding to the ?classical? intracellular estrogen receptors ERá and ERâ and subsequent gene activation, which is a slow event. However, there is overwhelming physiological evidence that estrogens have rapid effects in the brain and other non-neural tissues that do not involve these classical receptors but rather is thought to involve a plasma membrane localized estrogen receptor. Indeed, a novel compound called STX has been synthesized that selectively activates this membrane estrogen receptor and mediates many of the physiological processes ascribed to estrogen without the growth promoting effects. The structure of the membrane estrogen receptor is not yet known although aspects of its cell signaling properties have been elucidated. Therefore, this project aims to identify and clone the membrane estrogen receptor using well-established functional cloning strategies. The specific sites expressing the membrane estrogen receptor will be identified in the brain and non-neural tissues by our two neuroscience graduate students. Identification of the membrane estrogen receptor will break new ground and generate new approaches for studying estrogen biology in particular physiological functions (energy and bone homeostasis, temperature regulation, stress responses, circadian rhythms, sleep cycles, learning/memory and mood) that become dis-regulated in hypo-estrogenic states in females (e.g., menopause). In addition, students and fellows world-wide have utilized STX to probe the function of the membrane estrogen receptor in multiple tissues (brain, bone, liver, and pancreas) and will benefit tremendously from having the membrane estrogen receptor clone since the gene sequence of the cloned estrogen receptor will be deposited immediately in GeneBank for the broader research community. Therefore, cloning the membrane estrogen receptor will have an enormous benefit not only for neuroscientists but for students of life sciences worldwide.