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Updated: Jul 13, 2026
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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
Estrogen receptor alpha mediates estrogen-inducible abnormalities in the developing penis
H O Goyal1, T D Braden, P S Cooke
1Department of Biomedical Sciences, Tuskegee University, Tuskegee, AL 36088, USA. goyalho@tuskegee.edu
Reproduction (Cambridge, England)
|July 10, 2007
Summary
Neonatal exposure to diethylstilbestrol (DES) causes penile abnormalities in mice by upregulating estrogen receptor-alpha (ERalpha). ERalpha knockout mice showed no such effects, confirming ERalpha
Area of Science:
- Reproductive toxicology
- Endocrinology
- Developmental biology
Background:
- Neonatal exposure to diethylstilbestrol (DES) has been linked to adverse effects on male reproductive development.
- Estrogen receptor-alpha (ERalpha) upregulation was previously associated with these detrimental effects in rat penile development.
Purpose of the Study:
- To investigate the role of ERalpha in mediating the harmful effects of neonatal DES exposure on penile development.
- To test the hypothesis that ERalpha is the primary mediator of DES-induced penile abnormalities using an ERalpha knockout (ERalphaKO) mouse model.
Main Methods:
- ERalpha knockout (ERalphaKO) and wild-type C57BL/6 mice were administered oil or DES from postnatal days 2-12.
- Penile development, tissue morphology, fertility, and hormone levels were assessed in adulthood.
- Comparative analysis between DES-treated wild-type and ERalphaKO mice was performed.
Main Results:
- DES exposure caused significant penile malformations, reduced size, and muscle weight deficits in wild-type mice.
- ERalphaKO mice treated with DES exhibited no penile abnormalities, unlike their wild-type counterparts.
- Wild-type mice exposed to DES were infertile, while ERalphaKO mice were inherently infertile but maintained normal penile development.
Conclusions:
- Estrogen receptor-alpha plays an obligatory role in mediating the adverse effects of neonatal DES exposure on penile development.
- The ERalphaKO mouse model provides unequivocal evidence for ERalpha's essential function in DES-induced reproductive toxicity.
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