Modulation of oestrogen receptor signalling by association with the activated dioxin receptor View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-05

AUTHORS

Fumiaki Ohtake, Ken-ichi Takeyama, Takahiro Matsumoto, Hirochika Kitagawa, Yasuji Yamamoto, Keiko Nohara, Chiharu Tohyama, Andree Krust, Junsei Mimura, Pierre Chambon, Junn Yanagisawa, Yoshiaki Fujii-Kuriyama, Shigeaki Kato

ABSTRACT

Environmental contaminants affect a wide variety of biological events in many species. Dioxins are typical environmental contaminants that exert adverse oestrogen-related effects. Although their anti-oestrogenic actions are well described, dioxins can also induce endometriosis and oestrogen-dependent tumours, implying possible oestrogenic effects. However, the molecular mechanism underlying oestrogen-related actions of dioxins remains largely unknown. A heterodimer of the dioxin receptor (AhR) and Arnt, which are basic helix-loop-helix/PAS-family transcription factors, mediates most of the toxic effects of dioxins. Here we show that the agonist-activated AhR/Arnt heterodimer directly associates with oestrogen receptors ER-alpha and ER-beta. This association results in the recruitment of unliganded ER and the co-activator p300 to oestrogen-responsive gene promoters, leading to activation of transcription and oestrogenic effects. The function of liganded ER is attenuated. Oestrogenic actions of AhR agonists were detected in wild-type ovariectomized mouse uteri, but were absent in AhR-/- or ER-alpha-/- ovariectomized mice. Our findings suggest a novel mechanism by which ER-mediated oestrogen signalling is modulated by a co-regulatory-like function of activated AhR/Arnt, giving rise to adverse oestrogen-related actions of dioxin-type environmental contaminants. More... »

PAGES

545

References to SciGraph publications

  • 2005-06-21. Aryl hydrocarbon or dioxin receptor: Biologic and toxic responses in REVIEWS OF PHYSIOLOGY, BIOCHEMISTRY AND PHARMACOLOGY, VOLUME 94
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature01606

    DOI

    http://dx.doi.org/10.1038/nature01606

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1016710482

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12774124


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