Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells
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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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BPA is thought to be an endocrine disruptor that acts as an estrogen mimetic.
“BPA is thought to be an endocrine disruptor that acts as an estrogen mimetic [ 128–131 ], thus research has focused largely on its effects in reproductive tissues.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [128]
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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
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-02-27
- Volume
- 115
- Issue
- 6
- Pages
- 902-908
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1892114
- 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
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 3958 d)
- 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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