Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats

Abstract

Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO₂) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO₂-2,2′,3′,4′,5,6-hexachlorobiphenyl (3-MeSO₂-CB132); 3-MeSO₂-2,2′,3′,4′, 5,5′-hexachlorobiphenyl (3-MeSO₂-CB141); 3-MeSO₂-2,2′,4′,5,5′,6-hexachlorobiphenyl (3-MeSO₂-CB149) and 4-MeSO₂-2,2′,4′,5,5′,6-hexachlorobiphenyl (4-MeSO₂-CB149). The congeners were major MeSO₂-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO₂ metabolites (20 μmol/kg once daily for 4 days) reduced serum total thyroxine levels by 22–44% at a much lower dose than phenobarbital (PB; 431 μmol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO₂-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO₂-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO₂-CB132, 3-MeSO₂-CB141 and 3-MeSO₂-CB149, but not by 4-MeSO₂-CB149. Thus, it is likely that the 3-MeSO₂-hexachlorobiphenyls and 4-MeSO₂-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO₂ metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.