期刊
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
卷 20, 期 2, 页码 351-358出版社
WILEY
DOI: 10.1002/etc.5620200216
关键词
hydroxylated polychlorinated biphenyls; mixtures; vitellogenin; trout; endocrine disruption
资金
- NIEHS NIH HHS [ES-07060, ES-04766, ES-03850] Funding Source: Medline
Many natural and synthetic xenobiotics are known to interact with endocrine systems of animals. Various hydroxylated metabolites of persistent polychlorinated biphenyl contaminants (hydroxy-polychlorinated biphenyls [OH-PCBs]) have been shown to have agonist or antagonist interactions with estrogen receptors (ERs). In this study, 4-hydroxy-2',4',6'-trichlorobiphenyl (ON PCB 30) and 4-hydroxy-2',3',4',5'-tetrachlorobipheny (OH-PCB 61), and the natural estrogens 17 beta -estradiol (E-2) and estrone (E-1), were incorporated into diet and fed to juvenile rainbow trout. The production of vitellogenin (VTG), an egg yolk protein precursor in oviparous animals, was used as a marker of hepatic ER binding. All compounds induced plasma VTG in a dose-dependent manner, with maximal levels of approximately 5 mg VTG/ml plasma induced by E-2, E-1, and OH-PCB 30. Maximum plasma VTG of 0.048 mg/ml in the highest dose (50 mg/kg) of OH-PCB 61 was approximately 100-fold lower than natural estrogens and OH-PCB 30. At doses that induced submaximal VTG, E-1 was two- to threefold less potent, and OH-PCBs were up to 500-fold less potent, than E-2. Sex differences in VTG synthesis were apparent at weakly estrogenic doses, but not at maximal VTG-inducing doses. Predictions from previous receptor-binding studies underestimated the maximum estrogenic response of OH-PCB 30 in trout, which was achieved with a dose 10 times higher than E-2. Differences in plasma VTG induction by OH-PCB 30 and OH-PCB 61 support in vitro predictions that the degree and position of chlorination are important for ER activation. Neither mixtures of estrogens nor OH-PCBs resulted in synergistic VTG induction.
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