Cited by 142Effects and risks of endocrine disrupting chemicalsEstrogen and related hormone effectsProstate Cancer Treatment and Research

Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells

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Richter, Catherine A., Taylor, Julia A., Ruhlen, Rachel L., Welshons, Wade V., vom Saal, Frederick S.·2007·Environmental Health Perspectives

Abstract

Background: Hormonal alterations during development have lifelong effects on the prostate gland. Endogenous estrogens, including 17β-estradiol (E2), and synthetic estrogenic endocrine disruptors, such as bisphenol A (BPA), have similar effects on prostate development. Increasing exposure to estrogens within the low-dose, physiologic range results in permanent increases in the size and androgen responsiveness of the prostate, whereas exposure within the high-dose, pharmacologic range has the opposite effects. Objectives: We tested the hypothesis that the low-dose effects of estrogens on the developing prostate are associated with increased expression of androgen receptor (Ar) and estrogen receptor 1 (α) (Esr1) genes in mesenchyme cells. Methods: Ar and Esr1 mRNA levels were quantified in primary cultures of fetal mouse prostate mesenchyme cells treated with E2 and BPA. Discussion: Ar and Esr1 mRNA expression increased in response to E2, with thresholds of 0.001 and 0.037 nM, respectively; and in response to BPA, with a threshold of 1 nM for both mRNAs. We did not observe the expected inhibition of Ar mRNA expression by pharmacologic levels of E2 relative to unexposed cells. Conclusions: The observed induction of gene expression occurred at concentrations within the range of free E2 previously shown to permanently increase prostate size, thus supporting the involvement of direct effects of estrogens on gene expression in prostate mesenchyme. The effects of BPA occurred within the range of concentrations currently measured in human serum, demonstrating the vulnerability of developing tissues to xenoestrogens.

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Authors
Richter, C. A., Taylor, J. A., Ruhlen, R. L., Welshons, W. V., & vom Saal, F. S.
Affiliations
  • Division of Biological Sciences and
  • University of Missouri (US)
Venue
Environmental Health Perspectives
Published
2007-02-27
Volume
115
Issue
6
Pages
902-908
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
OpenAlex
W2128841974
Cited by
142
References
47
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 13 · 2016: 5 · 2015: 12 · 2014: 10 · 2013: 9 · 2012: 8
FWCI
5.06
Type
journal article
Language
en
Open access
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • MOspace Institutional Repository (University of Missouri) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences (ES-11283, P01ES010535, P01 ES 10535, R01ES011283, F32ES011549, 1F32ES-11549-01)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Keywords
estradiol, bisphenol A, androgen receptor, estrogen receptor alpha, prostate development, endocrine disruptors, xenoestrogens, gene expression, dose-response threshold
MeSH terms
Bisphenol A Compounds, Analysis of Variance, Animals, Benzhydryl Compounds, Dose-Response Relationship, Drug, Estradiol, Fetus, Male, Mesoderm, Phenols, Prostate, Receptors, Androgen, Receptors, Estrogen, DNA Primers, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, Mice

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