Non-genomic effects of endocrine disrupters: inhibition of estrogen sulfotransferase by phenols and chlorinated phenols.
Phenols are used world-wide and their presence in the environment is a cause of increasing concern. Despite evidence to suggest that, in general, they bind poorly to estrogen receptors, they are suspected of being endocrine disrupters. Here, we show that 2, x-substituted phenols are potent inhibitors of estrogen sulfotransferase with IC(50) values at low- or sub-micromolar levels. Our results demonstrate a potential non-genomic mechanism of action for these compounds and suggest that, where viable alternatives exist, both phenols substituted in the 2-position and their metabolic precursors should be avoided.
Harris
R M
RM
School of Biosciences, The University of Birmingham, Edgbaston, UK.
Kirk
C J
CJ
Waring
R H
RH
D002478:Cells, Cultured; D002733:Chlorophenols / Q000494:pharmacology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010636:Phenols / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000502:physiology
D002733:Chlorophenols; D052244:Endocrine Disruptors; D010636:Phenols; D015238:Sulfotransferases; C020122:estrone sulfotransferase