INHIBITION OF THYROID-HORMONE SULFATION BY HYDROXYLATED METABOLITES OF POLYCHLORINATED-BIPHENYLS

In this study we investigated the possible inhibitory effects of hydro xylated metabolites of polychlorinated biphenyls (OH-PCBs) on iodothyr onine 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 use d as the model substrate for the active hormone T3. An important struc tural requirement for T2 sulfotransferase inhibition is a hydroxyl gro up 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 developme nt and since hydroxylated PCBs can accumulate in fetuses, inhibition o f T3 sulfation could be a possible mechanism for the developmental neu rotoxicity of PCBs. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.