Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-, penta- and hexachlorinated biphenyls in male Sprague-Dawley rats.
Male Sprague-Dawley rats received four consecutive intraperitoneal doses of nine methylsulfonyl (MeSO2) metabolites of tetra-, penta- and hexachlorinated biphenyls (tetra-, penta- and hexaCBs) to determine their effects on thyroid hormone levels. Nine MeSO2 metabolites, 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), 4-MeSO2-2,2',4',5,5'-pentaCB (4-MeSO2-CB101), 3-MeSO2-2,2',3',4',5,6-hexaCB (3-MeSO2-CB132), 3-MeSO2-2,2',3',4',5,5'-hexaCB (3-MeSO2-CB141), 3-MeSO2-2,2',4',5,5',6-hexaCB (3-MeSO2-CB149) and 4-MeSO2-2,2',4',5,5',6-hexaCB (4-MeSO2-CB149). All nine MeSO2 metabolites (20 micromol/kg once daily for four days) reduced serum total thyroxine levels (16-44%) at a much lower dose than phenobarbital (431 micromol/kg once daily for four days) on days 2, 3, 4 and 7 after the last dosage. Total triiodothyronine level was reduced 37% by treatments with 3-MeSO2-CB49 and 3-MeSO2-CB149 at day 7, but increased 35% and 38% by 3-MeSO2-CB70 and 4-MeSO2-CB101 at days 3 and 4, respectively. The reductions in thyroxine levels led to an increase in thyroid-stimulating hormone levels by 3-MeSO2-CB49, 3-MeSO2-CB87, 3-MeSO2-CB101, 3-MeSO2-CB132, 3-MeSO2-CB141, 3-MeSO2-CB149 and 4-MeSO2-CB149. A 30% increase in thyroid weight was produced by 3-MeSO2-CB101 and 3-MeSO2-CB141 treatments. Total cytochrome P450 content and the activity of 7-pentoxyrosorufin O-dealkylase were increased by all seven 3-MeSO2-PCBs. 3-MeSO2-CB49, 3-MeSO2-CB87, 3-MeSO2-CB101 and 3-MeSO2-CB132 also increased the activity of 7-ethoxyresorufin O-dealkylase. Thus, it is likely that all nine tested MeSO2 metabolites could influence thyroid hormone metabolism. The results show that tested 3- and 4-MeSO2 metabolites of tetra-, penta- and hexaCBs reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.
Kato
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan. kato@ys7.u-shizuoka-ken.ac.jp
Haraguchi
K
K
Shibahara
T
T
Yumoto
S
S
Masuda
Y
Y
Kimura
R
R
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000493:pharmacokinetics / Q000494:pharmacology*; D013961:Thyroid Gland / Q000378:metabolism; D013974:Thyroxine / Q000097:blood*
D013450:Sulfones; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D013974:Thyroxine