New roles for neuronal estrogen receptors

Estrogens encompass steroid hormones which display physiological roles not only in the female reproductive system but also in other organ systems of non-reproductive controls, including the peripheral and central nervous systems. Traditionally, estrogen signals in neurons through a genomic pathway: binding to estrogen receptors (ERs) which then interact with nuclear estrogen response elements to initiate transcription. This effect is usually delayed at onset (within several hours to days) and prolonged in duration. In addition to these classical ERs, recent data suggest that other ERs function through pregenomic signaling pathways. Estrogen's pregenomic pathways cause intracellular changes within seconds to minutes and go through a novel, 7-transmembrane spanning G protein-coupled receptor (GPER, formerly known as GPR30). In this review, we will briefly cover the cellular and molecular mechanisms of GPER and then discuss newly discovered roles of GPER in cognition, depression, homeostasis, pain processing, and other associated neuronal functions.