ARTICLE NO. TX982504 In Vitro Inhibition of Thyroid Hormone Sulfation by Polychlorobiphenylols: Isozyme Specificity and Inhibition Kinetics

It was recently demonstrated by our laboratory that hydroxy-lated metabolites of polychlorinated biphenyls (PCB-OHs) are inhibitors of thyroid hormone sulfation. In this study, a more detailed investigation on sulfotransferase isozyme specificity and the kinetics of inhibition was performed. Thyroid hormone sulfa-tion was determined using 3,3'-diiodothyronine (T2) as a sub-strate, and various sources of sulfotransferase (SULT) enzyme were used; e.g., female and male rat liver cytosol, male brain cytosol and cytosolic preparations of V79 cells transfected with rat SULT1C1, and human SULT1A1 and human SULT1A3. The inhibition pattern and IC50 values were very similar for male and female rat liver and rSULTlCl and hSULTlAl. PCB-OHs were not able to inhibit the T2 sulfotranferase activity using hSULTlA3. Metabolite 3-hydroxy-2,3',4,4',5-pentachlorobiphenyl did not inhibit T2 sulfotransferase activity in male brain cytosol