EAGER: Cloning of a CNS Membrane Estrogen Receptor

Oregon Health & Science University, Portland OR

Investigators

Abstract

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.