Cell localization, physiology, and nongenomic actions of estrogen receptors

The existence of binding proteins for the female sex steroid, 17beta-estradiol, has been known for almost 50 years. Presently, two estrogen receptors (ERs), ER-alpha and ER-beta, have been cloned in mammals, and they are expressed in many cell types of metazoans. ERs act primarily as nuclear transcription factors, and this effect is enhanced by ligand binding. Emerging data have identified a separate pool of receptors for this steroid in the plasma membrane, but the mechanisms of action and cellular functions of these proteins are just beginning to be defined. In this review, the known details of the nuclear and plasma membrane ER functions will be discussed. A particular focus will be to define the signaling pathways from the membrane that lead to important cell physiology effects of estrogen. The potential interactions of membrane ER with other local proteins will also be discussed, and the unique but often complementary roles of the receptor pools will be highlighted. These details may be of additional relevance to other steroid receptors, since there is evidence of their existence in the cell membrane.