title: In vitro and in vivo estrogenic activity of chlorinated derivatives of bisphenol A.
abstract: The estrogenic activity of bisphenol A (BPA) and its chlorinated derivatives, 2-(3-chloro-4-hydroxyphenyl)-2-(4-hydroxyphenyl)propane (3-ClBPA) and 2,2-bis(3-chloro-4-hydroxyphenyl)propane (3,3'-diClBPA) was assessed by determining their relative binding affinity for the human estrogen receptor-alpha and -beta (ERalpha and ERbeta) and also their uterotrophic activity in ovariectomized female rats. BPA and its chlorinated derivatives were active in competing with [3H]17beta-estradiol for their binding to the human ERalpha and ERbeta proteins. While 3-ClBPA and 3,3'-diClBPA competed more effectively for ERalpha binding than BPA (IC50 values of 2.48x10(-5), 1.28x10(-5), and 1.08x10(-4)M, respectively), they had similar activity as BPA for competing the binding to ERbeta (IC50 values of 1.43x10(-5), 1.87x10(-5), and 2.59x10(-5)M, respectively). To determine the uterotropic activity, three doses (10, 50 and 100 mg/kg/day) of BPA and its derivatives were given to mature ovariectomized Sprague-Dawley rats for 3 consecutive days. Treatment of animals with 50 and 100 mg/kg/day of BPA or its chlorinated derivatives caused a significant increase in the uterine wet weight and the endometrial area. The results of our present study demonstrated that the affinities of 3-ClBPA and 3,3'-diClBPA for ERalpha were higher than the affinity of BPA, although the in vivo estrogenic activity of the two chlorinated BPAs in ovariectomized female Sprague-Dawley rats appeared to be comparable to that of BPA.
authors.affiliation: School of Nursing, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takemura
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Sayama
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Terao
authors.forename: Bao Ting
authors.initials: BT
authors.lastname: Zhu
authors.forename: Kayoko
authors.initials: K
authors.lastname: Shimoi
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001667:Binding, Competitive; D002713:Chlorine / Q000737:chemistry; D002733:Chlorophenols / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects / Q000502:physiology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002713:Chlorine; D002733:Chlorophenols; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C497827:2,2-bis(3-chloro-4-hydroxyphenyl)propane; C497826:2-(3-chloro-4-hydroxyphenyl)-2-(4-hydroxyphenyl)propane; C006780:bisphenol A; D000098826:Bisphenol A Compounds