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Neurogastroenterol Motil. 2017 Jul;29(7). doi: 10.1111/nmo.13121.

New roles for neuronal estrogen receptors.

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Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
University of California, Los Angeles.


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.


GPER; estrogen; neuronal function; pregenomic pathway

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