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<title lang=en>Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.</title>
<creator>Pinto, Caroline</creator>
<creator>Grimaldi, Marina</creator>
<creator>Boulahtouf, Abdelhay</creator>
<creator>Pakdel, Farzad</creator>
<creator>Brion, François</creator>
<creator>Aït-Aïssa, Sélim</creator>
<creator>Cavaillès, Vincent</creator>
<creator>Bourguet, William</creator>
<creator>Gustafsson, Jan-Ake</creator>
<creator>Bondesson, Maria</creator>
<creator>Balaguer, Patrick</creator>
<contributor>Department of Biology and Biochemistry ; University of Houston</contributor>
<contributor>Institut de recherche en cancérologie de Montpellier (IRCM) ; Université Montpellier 1 (UM1) - CRLCC Val d'Aurelle - Paul Lamarque - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université de Montpellier (UM)</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>Institut National de l'Environnement Industriel et des Risques (INERIS)</contributor>
<contributor>Centre de Biochimie Structurale [Montpellier] (CBS) ; Institut National de la Santé et de la Recherche Médicale (INSERM) - Université de Montpellier (UM) - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>Department of Biosciences and Nutrition ; Karolinska Institutet [Stockholm]</contributor>
<contributor>This study was funded by grants from Agence Nationale de la Recherche Contaminants, Ecosystèmes, Santé Project "BISCOT" 2010, by the P189 NEMO project financed by the French Ministry of Environment, the US - Environmental Protection Agency (grant number R834289), the Texas Emerging Technology Fund under Agreement 300 - 9 - 1958, the National Institutes of Health's National Institute of Environmental Health Sciences (grant number R21ES020036).</contributor>
<description>International audience</description>
<source>ISSN: 0041-008X</source>
<source>EISSN: 1096-0333</source>
<source>Toxicology and Applied Pharmacology</source>
<publisher>Elsevier</publisher>
<identifier>inserm-01067804</identifier>
<identifier>http://www.hal.inserm.fr/inserm-01067804</identifier>
<identifier>http://www.hal.inserm.fr/inserm-01067804/document</identifier>
<identifier>http://www.hal.inserm.fr/inserm-01067804/file/pintot_et_al._manuscript.pdf</identifier>
<source>http://www.hal.inserm.fr/inserm-01067804</source>
<source>Toxicology and Applied Pharmacology, Elsevier, 2014, 280 (1), pp.60-69. 〈10.1016/j.taap.2014.07.020〉</source>
<identifier>DOI : 10.1016/j.taap.2014.07.020</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.taap.2014.07.020</relation>
<identifier>PUBMED : 25106122</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/25106122</relation>
<language>en</language>
<subject lang=es>Estrogen receptors</subject>
<subject lang=es>zebrafish</subject>
<subject lang=es>selective estrogens</subject>
<subject lang=es>endocrine disruptors</subject>
<subject lang=es>reporter cell lines</subject>
<subject>[SDV.TOX] Life Sciences [q-bio]/Toxicology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>: Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.</description>
<date>2014-08-08</date>
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