Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra- and pentachlorinated biphenyls in male Sprague-Dawley rats.
Male Sprague-Dawley rats received four consecutive intraperitoneal (i.p.) 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 mumol/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.
D000818:Animals; D002849:Chromatography, Gas; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000737:chemistry / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*