title: 4-hydroxy-2',4',6'-trichlorobiphenyl and 4-hydroxy-2',3',4',5'-tetrachlorobiphenyl are estrogenic in rainbow trout.
abstract: 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 (OH-PCB 30) and 4-hydroxy-2',3',4',5'-tetrachlorobiphenyl (OH-PCB 61), and the natural estrogen 17 beta-estradiol (E2) and estrone (E1), 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 E2, E1, 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, E1 was two- to threefold less potent, and OH-PCBs were up to 500-fold less potent, than E2. 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 E2. 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.
authors.affiliation: Department of Environmental and Molecular Toxicology and Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Carlson
authors.forename: D E
authors.initials: DE
authors.lastname: Williams
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D008297:Male; D017686:Oncorhynchus mykiss; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D014819:Vitellogenins / Q000096:biosynthesis / Q000097:blood
chemical_list: D004968:Estrogens, Non-Steroidal; D014819:Vitellogenins; C105195:4-hydroxy-2',4',6'-trichlorobiphenyl; D011078:Polychlorinated Biphenyls; C427824:4-hydroxy-2',3',4'-5'-tetrachlorobiphenyl