Journal ArticleDOI
Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications
Jean-François Arnal,Françoise Lenfant,Raphaël Métivier,Gilles Flouriot,Daniel Henrion,Marine Adlanmerini,Coralie Fontaine,Pierre Gourdy,Pierre Chambon,Benita S. Katzenellenbogen,John A. Katzenellenbogen,John A. Katzenellenbogen,John A. Katzenellenbogen +12 more
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TLDR
The in vitro studies that are the basis of the 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 are summarized.Abstract:
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.read more
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Book ChapterDOI
Estrogen receptor signaling mechanisms.
TL;DR: This chapter addresses the molecular events governing regulation of gene expression via the nuclear estrogen receptors (ERα, and ERβ) and the membrane estrogen receptor (GPER1) and describes mechanisms of cross-talk between signaling cascades activated by both nuclear and membrane estrogen receptors.
Journal ArticleDOI
Mechanisms for estrogen receptor expression in human cancer.
TL;DR: The mechanisms underlying the aberrant expression of ER in breast cancer and other types of human tumors are complex, involving considerable alternative splicing of ERα and ERβ, transcription factors, epigenetic and post-transcriptional regulation of ER expression.
Journal ArticleDOI
Endocrine disrupting chemicals: Impact on human health, wildlife and the environment:
TL;DR: The objective of this review is to provide an overview of research on environmental aspects of endocrine disrupting chemicals and their effects on human health, based on evidence from animal and human studies.
Journal ArticleDOI
Estrogen Receptors and Endometriosis.
Elodie Chantalat,Marie-Cécile Valéra,Charlotte Vaysse,Emmanuelle Noirrit,Mariam Rusidzé,Ariane Weyl,Kelig Vergriete,Etienne Buscail,Philippe Lluel,Coralie Fontaine,Jean-François Arnal,Françoise Lenfant +11 more
TL;DR: The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation and to summarize the current understanding of the molecular and cellular mechanisms of action of ERs.
Journal ArticleDOI
Emerging Estrogenic Pollutants in the Aquatic Environment and Breast Cancer.
TL;DR: An overview of emerging estrogen-like compounds in the environment is provided, studies demonstrating their direct or indirect interactions with ERs are summed up, and their presence to the development of breast cancer is linked.
References
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Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial
Jacques E. Rossouw,Garnet L. Anderson,Ross L. Prentice,Andrea Z. LaCroix,Charles Kooperberg,Marcia L. Stefanick,Rebecca D. Jackson,Shirley A.A. Beresford,Barbara V. Howard,Karen C. Johnson,Jane Morley Kotchen,Judith K. Ockene +11 more
TL;DR: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
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The steroid and thyroid hormone receptor superfamily
TL;DR: A superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid is identified, suggesting mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
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The nuclear receptor superfamily: the second decade.
David J. Mangelsdorf,Carl S. Thummel,Miguel Beato,Peter Herrlich,Günther Schütz,Kazuhiko Umesono,Bruce Blumberg,Philippe Kastner,Manuel Mark,Pierre Chambon,Ronald M. Evans +10 more
TL;DR: This research presents a new probabilistic procedure called ‘spot-spot analysis’ to characterize the response of the immune system to the presence of E.coli.
Journal ArticleDOI
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Feng Yue,Audrey Kim,Yan-Yan Li,Yin-Zhong Shen,Ming Hu,Jun Liu,Bing Ren,Bing Ren +10 more
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
Journal ArticleDOI
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial
Garnet L. Anderson,Marian C. Limacher,Annlouise R. Assaf,Tamsen Bassford,Shirley A.A. Beresford,Henry R. Black,Denise E. Bonds,Robert L. Brunner,Robert G. Brzyski,Bette J. Caan,Rowan T. Chlebowski,J. David Curb,Margery Gass,Jennifer Hays,Gerardo Heiss,Susan L. Hendrix,Barbara V. Howard,Judith Hsia,F. Allan Hubbell,Rebecca D. Jackson,Karen C. Johnson,Howard L. Judd,Jane Morley Kotchen,Lewis H. Kuller,Andrea Z. LaCroix,Dorothy S. Lane,Robert Langer,Norman L. Lasser,Cora E. Lewis,JoAnn E. Manson,Karen L. Margolis,Judith K. Ockene,Mary Jo O'Sullivan,Lawrence S. Phillips,Ross L. Prentice,Cheryl Ritenbaugh,John A Robbins,Jacques E. Rossouw,Gloria E. Sarto,Marcia L. Stefanick,Linda Van Horn,Jean Wactawski-Wende,Robert B. Wallace,Sylvia Wassertheil-Smoller +43 more
TL;DR: The use of conjugated equine estrogen (CEE) increases the risk of stroke, decreases therisk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years, indicating no overall benefit.