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Assessment of the Effects of Endocrine Disrupting Compounds on the Development of Vertebrate Neural Network Function Using Multi-electrode Arrays
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Bisphenol A affects androgen receptor function via multiple mechanisms.

Christina Teng1, Bonnie Goodwin, Keith Shockley

  • 1DNTP Biomolecular Screening Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, NC, USA. teng1@niehs.nih.gov

Chemico-Biological Interactions
|April 9, 2013
PubMed
Summary
This summary is machine-generated.

Bisphenol A (BPA) and its analog BPAF activate the estrogen receptor alpha (ERα) and block the androgen receptor (AR). Bisphenol S (BPS) shows weak ERα activity and does not affect AR. These findings clarify BPA's reproductive toxicity mechanisms.

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Assessment of the Effects of Endocrine Disrupting Compounds on the Development of Vertebrate Neural Network Function Using Multi-electrode Arrays
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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants

Published on: March 6, 2018

Area of Science:

  • Endocrinology
  • Toxicology
  • Molecular Biology

Background:

  • Bisphenol A (BPA) is an endocrine disruptor affecting reproductive systems, but its molecular mechanisms are not fully understood.
  • Nuclear receptors play critical roles in reproductive health and are targets for endocrine-disrupting compounds.

Purpose of the Study:

  • To investigate the molecular mechanisms by which BPA and its analogs (BPAF, BPS) interact with nuclear receptors.
  • To elucidate the effects of BPA on estrogen receptor alpha (ERα) and androgen receptor (AR) signaling pathways.

Main Methods:

  • Quantitative high-throughput screening (qHTS) of BPA against ten nuclear receptors.
  • Transient transfection assays using full-length ERα and AR with luciferase reporters.
  • Nuclear translocation assays using EGFP-tagged receptors.

Main Results:

  • BPA and BPAF are ERα agonists and AR antagonists, competitively inhibiting R1881 binding.
  • BPS exhibits weak ERα activity and does not antagonize AR.
  • BPA enhances ERα nuclear translocation but reduces AR nuclear translocation, indicating partial agonism for ERα and antagonism for AR.

Conclusions:

  • BPA and BPAF exhibit distinct and opposing effects on ERα and AR signaling pathways.
  • The findings provide molecular insights into the reproductive toxicity of BPA and its analogs.
  • Understanding these interactions is crucial for assessing the health risks associated with bisphenol exposure.