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

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 17beta-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 microg, 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 ERbeta have to be characterized in further investigations.

journal_name

Arch Toxicol

journal_title

Archives of toxicology

authors

Schmidt S,Degen GH,Seibel J,Hertrampf T,Vollmer G,Diel P

doi

10.1007/s00204-006-0102-4

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

839-45

issue

eissn

0340-5761

issn

1432-0738

journal_volume

pub_type

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