Pure estrogenic effect of benzophenone-2 (BP2) but not of bisphenol A (BPA) and dibutylphtalate (DBP) in uterus, vagina and bone.
Contradictory results whether the endocrine disrupters (ED) benzophenone-2 (BP2), bisphenol A (BPA) and dibutylphtalate (DBP) exert estrogenic effects have been published. Selective estrogen receptor modulators (SERMs) exert estrogenic effects in some but not in all organs and ED may be SERMs. Therefore, we studied their binding properties to recombinant ERalpha and ERbeta protein and their effects in the uterus, vagina and bone of ovariectomized rats. BP2 bound to both receptor subtypes, while BPA had a relatively high ERbeta selectivity. DBP did not bind to ERalpha but with a low affinity to ERbeta. In the uterus, only E2 and BP2 increased uterine weight and the complement C3 but decreased ERbeta gene expression. Discrete effects of BPA and DBP in the uterus were found upon histological examination. In the vagina, BP2 but not BPA and DBP had clear estrogenic effects. E2 and BP2 had antiosteoporotic effects in the metaphysis of the tibia. The serum surrogate parameters of bone metabolism, i.e. osteocalcin and the cross (rat) laps were significantly reduced by E2, an effect shared with BP2 but not by the two other EDs.


CONCLUSIONS
BP2 acts as ERalpha and ERbeta agonist mimicking effects of E2, while the effects of BPA and DBP are not pure estrogenic.
Seidlová-Wuttke
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Abt. Klin. und Exp. Endokrinologie, Universitäts-Frauenklinik Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. ufkendo@med.uni-goettingen.de
Jarry
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Wuttke
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D000818:Animals; D001559:Benzhydryl Compounds; D001577:Benzophenones / Q000633:toxicity*; D001842:Bone and Bones / Q000187:drug effects*; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects*; D014621:Vagina / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D001577:Benzophenones; D003993:Dibutyl Phthalate; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C035476:2,2',4,4'-tetrahydroxybenzophenone