Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs
January 2000
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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.
- In Vitro
- Humans
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
- Kinetics
- Biological Availability
- Hydroxylation
- Environmental Pollutants/*pharmacology
- Sulfotransferases/*antagonists & inhibitors
- Polychlorinated Biphenyls/*pharmacology
- Estradiol/pharmacokinetics
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