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.
Kester
M H
MH
Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
Bulduk
S
S
Tibboel
D
D
Meinl
W
W
Glatt
H
H
Falany
C N
CN
Coughtrie
M W
MW
Bergman
A
A
Safe
S H
SH
Kuiper
G G
GG
Schuur
A G
AG
Brouwer
A
A
Visser
T J
TJ
D001682:Biological Availability; D004785:Environmental Pollutants / Q000494:pharmacology*; D004958:Estradiol / Q000493:pharmacokinetics; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*
D004785:Environmental Pollutants; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D015238:Sulfotransferases; C020122:estrone sulfotransferase