Takemura Hitomi, Ma Jie, Sayama Kazutoshi, Terao Yoshiyasu, Zhu Bao Ting, Shimoi Kayoko
School of Nursing, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Toxicology. 2005 Feb 14;207(2):215-21. doi: 10.1016/j.tox.2004.09.015.
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.
通过测定双酚A（BPA）及其氯化衍生物2-（3-氯-4-羟基苯基）-2-（4-羟基苯基）丙烷（3-ClBPA）和2,2-双（3-氯-4-羟基苯基）丙烷（3,3'-二氯双酚A）与人雌激素受体α和β（ERα和ERβ）的相对结合亲和力，以及它们在去卵巢雌性大鼠中的子宫营养活性，评估了它们的雌激素活性。BPA及其氯化衍生物在与[3H]17β-雌二醇竞争结合人ERα和ERβ蛋白方面具有活性。虽然3-ClBPA和3,3'-二氯双酚A比BPA更有效地竞争ERα结合（IC50值分别为2.48×10^(-5)、1.28×10^(-5)和1.08×10^(-4)M），但它们在竞争结合ERβ方面与BPA具有相似的活性（IC50值分别为1.43×10^(-5)、1.87×10^(-5)和2.59×10^(-5)M）。为了确定子宫营养活性，将三种剂量（10、50和100mg/kg/天）的BPA及其衍生物连续3天给予成熟的去卵巢Sprague-Dawley大鼠。用50和100mg/kg/天的BPA或其氯化衍生物处理动物会导致子宫湿重和子宫内膜面积显著增加。我们目前的研究结果表明，3-ClBPA和3,3'-二氯双酚A对ERα的亲和力高于BPA，尽管两种氯化双酚A在去卵巢雌性Sprague-Dawley大鼠中的体内雌激素活性似乎与BPA相当。
