title: Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs.
abstract: Polychlorinated biphenyls (PCBs) are persistent environmental pollutants which exert a variety of toxic effects in animals, including disturbances of sexual development and reproductive function. The estrogenic effects of PCBs may be mediated in part by hydroxylated PCB metabolites (PCB-OHs), but the mechanisms by which they are brought about are not understood. PCBs as well as PCB-Hs show low affinities for both alpha and beta estrogen receptor isoforms. In the present study we demonstrate that various environmentally relevant PCB-OHs are extremely potent inhibitors of human estrogen sulfotransferase, strongly suggesting that they indirectly induce estrogenic activity by increasing estradiol bioavailability in target tissues.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Kester
authors.forename: S
authors.initials: S
authors.lastname: Bulduk
authors.forename: D
authors.initials: D
authors.lastname: Tibboel
authors.forename: W
authors.initials: W
authors.lastname: Meinl
authors.forename: H
authors.initials: H
authors.lastname: Glatt
authors.forename: C N
authors.initials: CN
authors.lastname: Falany
authors.forename: M W
authors.initials: MW
authors.lastname: Coughtrie
authors.forename: A
authors.initials: A
authors.lastname: Bergman
authors.forename: S H
authors.initials: SH
authors.lastname: Safe
authors.forename: G G
authors.initials: GG
authors.lastname: Kuiper
authors.forename: A G
authors.initials: AG
authors.lastname: Schuur
authors.forename: A
authors.initials: A
authors.lastname: Brouwer
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D001682:Biological Availability; D004785:Environmental Pollutants / Q000494:pharmacology*; D004958:Estradiol / Q000493:pharmacokinetics; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*
chemical_list: D004785:Environmental Pollutants; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D015238:Sulfotransferases; C020122:estrone sulfotransferase