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Hormonal activity of combinations of genistein, bisphenol A and 17β-estradiol in the female Wistar rat

  • Organ Toxicity and Mechanisms
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Abstract

Phytoestrogens have been described as weak estrogens,selective estrogen receptor mediators (SERMs) or to exhibit antiestrogenic properties. However, information about their activity in combination with xenoestrogens and 17β-estradiol in vivo, is limited. Therefore, the combinatory activity of the phytoestrogen genistein (Gen), the industrial chemical bisphenol A (BPA), and ethinylestradiol (EE) in ovariectomized Wistar rats was analyzed in this study. All compounds were administered orally on three consecutive days (EE at 30 μg, Gen at 100 mg and BPA at 200 mg per kg body weight per day). The pure antiestrogen fulvestrant (3 mg/kg) served as estrogen receptor (ER) antagonist control. Effects on uterine wet weight, height of the uterine epithelium, uterine clusterin (Clu) and complement C3 expression, and the height of the vaginal epithelium were examined. Treatment with Gen alone resulted in a moderate stimulation of uterine weight; in the vagina the height of the epithelium was strongly stimulated. BPA did not stimulate any of the above-mentioned parameters significantly. In combination with EE, Gen acted on most of the analyzed parameters in an additive manner, whereas BPA significantly antagonized the effects of EE on the uterine epithelium and uterine Clu expression. Given in combination with Gen, BPA was also able to antagonize the stimulatory effect of Gen on the uterine epithelium. In summary, our results demonstrate that Gen, in contrast to BPA, does not exhibit any antiestrogenic properties, even if given at high concentrations. The results of this study characterize BPA as a functional antiestrogen, very likely the result of a lack of ability to activate ER-mediated transactivation after binding to the receptor. This is not the case for Gen. Our results point to the involvement of complex molecular mechanisms in the action of Gen. These mechanisms, especially the role of ERβ have to be characterized in further investigations.

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Acknowledgments

We thank Ute Laudenbach-Leschowsky for brilliant technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft grants Di 716/9–1 and Vo 410/6–3

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Authors and Affiliations

  1. Institut Kreislaufforschung und für Sportmedizin, Abt. Molekulare und Zelluläre Sportmedizin, Deutsche Sporthochschule Köln, Carl-Diem-Weg 6, 50933, Cologne, Germany

    Simone Schmidt, Jan Seibel, Torsten Hertrampf & Patrick Diel

  2. Institut für Arbeitsphysiologie an der Universität Dortmund, Dortmund, Germany

    Gisela H. Degen

  3. Institut für Zoologie, Lehrstuhl für molekulare und zelluläre Endokrinologie, Technische Universität Dresden, Dresden, Germany

    Günter Vollmer

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  1. Simone Schmidt
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  2. Gisela H. Degen
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  4. Torsten Hertrampf
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  5. Günter Vollmer
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Correspondence to Patrick Diel.

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Schmidt, S., Degen, G.H., Seibel, J. et al. Hormonal activity of combinations of genistein, bisphenol A and 17β-estradiol in the female Wistar rat. Arch Toxicol 80, 839–845 (2006). https://doi.org/10.1007/s00204-006-0102-4

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  • DOI: https://doi.org/10.1007/s00204-006-0102-4

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