title: Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro.
abstract: Estrogen receptor (ER) antagonistic chemicals in aquatic environments are believed to influence the binding of both endogenous and exogenous estrogens to ERs in aquatic organisms. Although the combined effects of estrogenic compounds have attracted much scientific concern, little work has been done on the influence of such antiestrogens on the biological effects of estrogens. This study focused on how the presence of different amounts of antagonists affects the results of ER agonist activity tests. To achieve this, three questions were stated and answered in sequence. A two-hybrid recombinant yeast assay mediated by ER was adopted, providing a single mode of action and single target of action for this study. Mixtures created by an ER agonist and three antagonists following the fixed-ratio principle were assessed. The concentration of 17β-estradiol causing maximum induction was set as the fixed dose of estrogen in the antagonist activity test (question 1). When the two classes of chemicals coexisted, antiestrogens, which as a whole behaved according to the concentration addition model (question 2), decreased the response of estrogen and compressed the concentration-response curves along the y-axis in the agonist activity test (question 3). This may cause the estradiol equivalent to be underestimated and potentially mask the action of estrogenic effects in toxicity evaluation of environmental samples.
authors.affiliation: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Rao
authors.affiliation: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China. Electronic address: mamei@rcees.ac.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Ma
authors.affiliation: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China. Electronic address: wangzj@rcees.ac.cn.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Wang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000737:chemistry; D004965:Estrogen Antagonists / Q000633:toxicity*; D020847:Estrogen Receptor Modulators / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D010575:Pesticides / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D010575:Pesticides; D004958:Estradiol; D001616:beta-Galactosidase
keywords: Antiestrogen; Estrogen; Mixture toxicity; Prediction model; Two-hybrid yeast bioassay