دورية أكاديمية
The tissue-specific effects of different 17β-estradiol doses reveal the key sensitizing role of AF1 domain in ERα activity
| العنوان: | The tissue-specific effects of different 17β-estradiol doses reveal the key sensitizing role of AF1 domain in ERα activity |
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| المؤلفون: | Fontaine, Coralie, Buscato, Melissa, Vinel, Alexia, Giton, Frank, Raymond-Letron, Isabelle, Kim, Sung Hoon, Katzenellenbogen, Benita S, Katzenellenbogen, John A, Gourdy, Pierre, Milon, Alain, Flouriot, Gilles, Ohlsson, Claes, Lenfant, Françoise, Arnal, Jean-François |
| المساهمون: | Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), University of Illinois at Urbana-Champaign Urbana (UIUC), University of Illinois System, Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-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 ), École des Hautes Études en Santé Publique EHESP (EHESP), Institut National de la Santé et de la Recherche Médicale, Université de Toulouse, Fondation pour la Recherche Médicale, 00086486, Fondation de France, Agence Nationale de la Recherche, Centre National de la Recherche Scientifique, Ligue Contre le Cancer, NIH R01 DK015556, National Institutes of Health, BCRF 18–082, Breast Cancer Research Foundation, University of Rennes1 |
| المصدر: | ISSN: 0303-7207. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2020 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | Tissue-specific, Activation function (AF), Dose response, Estrogen receptor alpha (ERα), [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| الوصف: | International audience ; 17β-Estradiol (E2) action can be mediated by the full-length estrogen receptor alpha (ERα66), and also by the AF1 domain-deficient ERα (ERα46) isoform, but their respective sensitivity to E2 is essentially unknown. We first performed a dose response study using subcutaneous home-made pellets mimicking either metestrus, proestrus or a pharmacological doses of E2, which resulted in plasma concentrations around 3, 30 and 600 pM, respectively. Analysis of the uterus, vagina and bone after chronic exposure to E2 demonstrated dose-dependent effects, with a maximal response reached at the proestrus-dose in wild type mice expressing mainly ERα66. In contrast, in transgenic mice harbouring only an ERα deleted in AF1, these effects of E2 were either strongly shifted rightward (10-100-fold) and/or attenuated, depending on the tissue studied. Finally, experiments in different cell lines transfected with ERα66 or ERα46 also delineated varying profiles of ERα AF1 sensitivity to E2. Altogether, this work emphasizes the importance of dose in the tissue-specific actions of E2 and demonstrates the key sensitizing role of AF1 in ERα activity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32004676; hal-02470890; https://univ-rennes.hal.science/hal-02470890Test; https://univ-rennes.hal.science/hal-02470890/documentTest; https://univ-rennes.hal.science/hal-02470890/file/Fontaine%20et%20al-2020-The%20tissue-specific%20effects%20of%20different%2017%CE%B2-estradiol%20doses%20reveal%20the%20key.pdfTest; PUBMED: 32004676 |
| DOI: | 10.1016/j.mce.2020.110741 |
| الإتاحة: | https://doi.org/10.1016/j.mce.2020.110741Test https://univ-rennes.hal.science/hal-02470890Test https://univ-rennes.hal.science/hal-02470890/documentTest https://univ-rennes.hal.science/hal-02470890/file/Fontaine%20et%20al-2020-The%20tissue-specific%20effects%20of%20different%2017%CE%B2-estradiol%20doses%20reveal%20the%20key.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.D06256AC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.mce.2020.110741 |
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