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Updated: Jun 3, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system

Fumiaki Ohtake1, Yoshiaki Fujii-Kuriyama, Kaname Kawajiri

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

The Journal of Steroid Biochemistry and Molecular Biology
|March 15, 2011
PubMed

Insights

Environmental chemicals like dioxins interact with the aryl hydrocarbon receptor (AhR) to alter estrogen and androgen signaling. AhR directly associates with estrogen (ER) and androgen (AR) receptors, affecting gene expression and promoting receptor degradation.

Area of Science:

  • Endocrinology
  • Environmental Toxicology
  • Molecular Biology

Background:

  • The aryl hydrocarbon receptor (AhR) is a transcription factor mediating dioxin toxicity.
  • Cross-talk between dioxins and estrogen/androgen signaling pathways is known but poorly understood.
  • Molecular mechanisms of dioxin-mediated modulation of steroid hormone signaling remain largely elusive.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying dioxin-mediated modulation of estrogen and androgen signaling pathways.
  • To investigate the direct interactions between the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) or androgen receptor (AR).
  • To explore the role of AhR in both genomic and non-genomic regulation of ER and AR.

Main Methods:

  • Investigated direct physical association between AhR and ER/AR.
  • Analyzed the functional consequences of AhR-ER complex formation on target gene expression.
  • Examined the role of AhR in mediating non-genomic effects via the ubiquitin-proteasome system.
  • Identified components of the ubiquitin ligase complex involved in AhR-mediated degradation of ER and AR.

Main Results:

  • Dioxins modulate estrogen and androgen signaling partly through direct association of AhR with ER and AR.
  • Agonist-bound AhR and ERα form a functional unit regulating target gene expression (genomic action).
  • AhR mediates non-genomic actions by assembling a CUL4B-based ubiquitin ligase complex, promoting ERα and AR degradation.

Conclusions:

  • AhR plays a dual role in regulating ER and AR signaling through both genomic and non-genomic mechanisms.
  • The ubiquitin system is crucial for sensing and responding to environmental chemicals like dioxins.
  • AhR functions as a component of a ubiquitin ligase, enhancing the degradation of ER and AR in response to environmental stimuli.

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