Related Experiment Video

Updated: Jun 24, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Modulation of oestrogen receptor signalling by association with the activated dioxin receptor

Fumiaki Ohtake1, Ken-ichi Takeyama, Takahiro Matsumoto

  • 1The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.

Nature
|May 30, 2003
PubMed

Insights

Dioxins, environmental contaminants, can mimic estrogen's effects by interacting with estrogen receptors (ERs). Activated dioxin receptors (AhR) bind to ERs, influencing gene transcription and causing adverse estrogenic actions.

Area of Science:

  • Environmental toxicology
  • Molecular endocrinology
  • Gene regulation

Background:

  • Environmental contaminants like dioxins exhibit complex interactions with biological systems.
  • Dioxins are known for anti-estrogenic effects, but can also promote estrogen-dependent conditions, suggesting a dual role.
  • The precise molecular mechanisms behind dioxin-induced estrogen-related effects remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular mechanism by which dioxins exert estrogen-related effects.
  • To determine if the dioxin receptor (AhR) pathway interacts with estrogen receptor (ER) signaling.
  • To elucidate how AhR/Arnt heterodimers modulate estrogen-responsive gene transcription.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions between AhR/Arnt and ERs.
  • Chromatin immunoprecipitation (ChIP) to identify binding of AhR/Arnt and ERs to target gene promoters.
  • Quantitative PCR and Western blotting to assess gene expression and protein levels.
  • In vivo studies using wild-type and knockout (AhR-/-, ER-alpha-/-) ovariectomized mice to evaluate estrogenic responses in uterine tissue.

Main Results:

  • The activated AhR/Arnt heterodimer directly associates with both ER-alpha and ER-beta.
  • This interaction facilitates the recruitment of unliganded ER and the co-activator p300 to estrogen-responsive gene promoters.
  • The activated AhR/Arnt complex leads to the activation of transcription and exhibits estrogenic effects, while attenuating the function of liganded ER.
  • Estrogenic effects of AhR agonists were observed in wild-type mice but were abolished in AhR-/- or ER-alpha-/- mice.

Conclusions:

  • Activated AhR/Arnt functions as a co-regulator, directly modulating ER-mediated estrogen signaling.
  • This novel mechanism explains the adverse estrogen-related actions of dioxin-type environmental contaminants.
  • The findings reveal a critical link between dioxin exposure and endocrine disruption through direct interaction with the estrogen receptor pathway.

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