Cellular functions of plasma membrane estrogen receptors

Strong evidence now exists for the presence and importance of plasma membrane estrogen receptors (ER) in a variety of cells that are targets for steroid action. When estradiol (E2) binds cell surface proteins, the initiation of signal transduction triggers downstream signaling cascades that contribute to important functions. These functions include cell growth and survival, migration, and new blood vessel formation. In some instances these effects result from the initiation of gene transcription, upregulated through signaling from the membrane. The membrane ER probably originates from the same gene and transcript that produces the nuclear receptor. In the membrane, ER appear to localize mainly to discrete domains of the plasma membrane, known as caveolae, but the mechanisms by which this small pool of ER translocates to this site are currently unknown. At the caveolae, a cross talk with signaling molecules facilitates E2/ER cell biologic actions. This both includes direct stimulation of signaling via G protein activation, and a cross-activation of the epidermal growth factor receptor (EGFR). This review article highlights some of the important advances in understanding the cell biology of estrogen action that emanates from the membrane.