Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats.
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 micromol/kg once daily for 4 days) reduced serum total thyroxine levels by 22-44% at a much lower dose than phenobarbital (PB; 431 micromol/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.
Kato
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Haraguchi
K
K
Shibahara
T
T
Masuda
Y
Y
Kimura
R
R
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003864:Depression, Chemical; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008698:Mesylates / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology; D013963:Thyroid Hormones / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood
D006993:Hypnotics and Sedatives; D008698:Mesylates; D013963:Thyroid Hormones; D014284:Triiodothyronine; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010634:Phenobarbital