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 wh ich exert a variety of toxic effects in animals, including disturbances of sexual development and reproductive function. The estrogenic effects of PCB s may be mediated in part by hydroxylated PCB metabolites (PCB-OHs), but th e mechanisms by which they are brought about are not understood. PCBs as we ll as PCB-OHs 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 sulfotr ansferase, strongly suggesting that they indirectly induce estrogenic activ ity by increasing estradiol bioavailability in target tissues.