Inhibition of thyroid hormone sulfation by hydroxylated metabolites of polychlorinated biphenyls.
In this study we investigated the possible inhibitory effects of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) on iodothyronine sulfotransferase activity. The results indicate that OH-PCBs are potent inhibitors of this activity in vitro, with IC50 concentrations in the low micro molar range. Inhibition of sulfotransferase activity towards 3,3'-diiodothyronine (T2) was similar to that towards 3,3',5-triiodothyronine (T3) in this in vitro assay, therefore, T2 can be used as the model substrate for the active hormone T3. An important structural requirement for T2 sulfotransferase inhibition is a hydroxyl group on the para or meta position of the OH-PCBs. Since T3 is the active hormone, playing a very important role in somatic and brain development and since hydroxylated PCBs can accumulate in fetuses, inhibition of T3 sulfation could be a possible mechanism for the developmental neurotoxicity of PCBs.
Schuur
A G
AG
Department of Toxicology, Agricultural University Wageningen, The Netherlands. gerlienke.schuur@algemeen.tox.wau.nl
Brouwer
A
A
Bergman
A
A
Coughtrie
M W
MW
Visser
T J
TJ
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004104:Diiodothyronines / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology; D008297:Male; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
D004104:Diiodothyronines; D013431:Sulfates; D013963:Thyroid Hormones; C030629:3,3'-diiodothyronine; D011078:Polychlorinated Biphenyls; D015238:Sulfotransferases; C109377:iodothyronine sulfotransferase