Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs

Endocrinology. 2000 May;141(5):1897-900. doi: 10.1210/endo.141.5.7530.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biological Availability
  • Environmental Pollutants / pharmacology*
  • Estradiol / pharmacokinetics
  • Humans
  • Hydroxylation
  • In Vitro Techniques
  • Kinetics
  • Polychlorinated Biphenyls / pharmacology*
  • Sulfotransferases / antagonists & inhibitors*

Substances

  • Environmental Pollutants
  • Estradiol
  • Polychlorinated Biphenyls
  • Sulfotransferases
  • estrone sulfotransferase