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<title lang=en>Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications</title>
<creator>Arnal, Jean-François</creator>
<creator>Lenfant, Françoise</creator>
<creator>Métivier, Raphaël</creator>
<creator>Flouriot, Gilles</creator>
<creator>Henrion, Daniel</creator>
<creator>Adlanmerini, Marine</creator>
<creator>Fontaine, Coralie</creator>
<creator>Gourdy, Pierre</creator>
<creator>Chambon, Pierre</creator>
<creator>Katzenellenbogen, Benita</creator>
<creator>Katzenellenbogen, John</creator>
<contributor>Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) ; Université Paul Sabatier - Toulouse 3 (UPS) - Hôpital de Rangueil - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<contributor>Institut de Génétique et Développement de Rennes (IGDR) ; Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Biologie Neurovasculaire et Mitochondriale Intégrée ; Université d'Angers (UA) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>Department of Molecular and Integrative Physiology ; University of Illinois and College of Medicine</contributor>
<contributor>Department of Chemistry ; University of Illinois at Urbana-Champaign [Urbana]</contributor>
<description>International audience</description>
<source>Physiological Reviews</source>
<identifier>hal-01533249</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533249</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533249</source>
<source>Physiological Reviews, 2017, 97 (3), pp.1045-1087. 〈10.1152/physrev.00024.2016〉</source>
<identifier>DOI : 10.1152/physrev.00024.2016</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1152/physrev.00024.2016</relation>
<identifier>PUBMED : 28539435</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/28539435</relation>
<language>en</language>
<subject>[SDV.GEN] Life Sciences [q-bio]/Genetics</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.</description>
<date>2017</date>
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