title: Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.
abstract: 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.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier, France.
authors.forename: Abdelhay
authors.initials: A
authors.lastname: Boulahtouf
authors.affiliation: Institut de Recherche sur la Santé, Environnement et Travail (IRSET), INSERM U1085, Université de Rennes 1, Rennes, France.
authors.forename: Farzad
authors.initials: F
authors.lastname: Pakdel
authors.affiliation: Unité Écotoxicologie In Vitro et In Vivo, INERIS, Parc ALATA, 60550 Verneuil-en-Halatte, France.
authors.forename: François
authors.initials: F
authors.lastname: Brion
authors.affiliation: Unité Écotoxicologie In Vitro et In Vivo, INERIS, Parc ALATA, 60550 Verneuil-en-Halatte, France.
authors.forename: Sélim
authors.initials: S
authors.lastname: Aït-Aïssa
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cavaillès
authors.affiliation: U1054, Centre de Biochimie Structurale, CNRS UMR5048, Université Montpellier 1 et 2, 34290 Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Bourguet
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056, USA; Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Bondesson
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier, France. Electronic address: patrick.balaguer@inserm.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D017930:Genes, Reporter / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen
keywords: Endocrine disruptors; Estrogen receptors; Reporter cell lines; Selective estrogens; Zebrafish
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