Publication | Open Access
Potent Inhibition of Estrogen Sulfotransferase by Hydroxylated PCB Metabolites: A Novel Pathway Explaining the Estrogenic Activity of PCBs
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2000
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Estradiol BioavailabilityFemale Reproductive FunctionReproductive EndocrinologyMolecular PharmacologyBiosynthesisRelevant Pcb-ohsToxicologyHydroxylated Pcb MetabolitesSteroid MetabolismEstrogenic ActivityBiochemistryHormonal ReceptorAromataseEcotoxicologyMetabolomicsEndocrinologyPharmacologyOvarian HormoneEndocrine DisruptorsPotent InhibitionMedicineEndocrine Research
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-OHs show low affinities for both α and β 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.