Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs
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.
|Keywords||Biological Availability, Environmental Pollutants/*pharmacology, Estradiol/pharmacokinetics, Humans, Hydroxylation, In Vitro, Kinetics, Polychlorinated Biphenyls/*pharmacology, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Sulfotransferases/*antagonists & inhibitors|
Kester, M.H.A., Bergman, A., Safe, S.H., Visser, T.J., Brouwer, A., Schuur, A.G., … Kuiper, G.G.J.M.. (2000). Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology. Retrieved from http://hdl.handle.net/1765/9366