Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra- and pentachlorinated biphenyls in male Sprague-Dawley rats

Abstract

Male Sprague-Dawley rats received four consecutive intraperitoneal (ip) doses of five kinds of methylsulfonyl (MeSO2) metabolites of tetra- and pentachlorinated biphenyls (tetra- and pentaCBs) to determine their effects on thyroid hormone levels. The five MeSO2 metabolites, which were the major MeSO2-PCBs detected in human milk, liver and adipose tissue were 3-MeSO2- 2,2',4',5-tetraCB (3-MeSO2-CB49), 3-MeSO2-2,3',4',5-tetraCB (3-MeSO2- CB70), 3-MeSO2-2,2',3',4',5-pentaCB (3-MeSO2-CB87), 3-MeSO2-2,2',4',5,5'- pentaCB (3-MeSO2-CB101), and 4-MeSO2-2,2',4',5,5'-pentaCB (4-MeSO2- CB101). All five tested MeSO2 metabolites (20 μmol/kg once daily for 4 days) reduced serum total thyroxine levels 16-40% on days 2, 3, 4, and 7 (after the last dosage). The total triiodothyronine level was reduced 37% by treatment with 3-MeSO2-CB49 at day 7, but was increased 35% and 38% by 3- MeSO2-CB70 and 4-MeSO2-CB101 at days 3 and 4, respectively. The reductions in thyroid hormone levels led to an increase in thyroid stimulating hormone (TSH) levels by 3-MeSO2-CB49, 3-MeSO2-CB87 and 3-MeSO2-CB101. A 30% increase in thyroid weight was produced by 3-MeSO2-CB101 treatment. Thus, it is likely that all five tested MeSO2 metabolites could influence thyroid hormone metabolism. The results show that the tested 3-and 4-MeSO2 metabolites of tetra- and pentaCBs reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.