ＰＣＢ類による甲状腺ホルモンかく乱作用とその作用機構：動物種差

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  • Species differences among mice, hamsters, rats and guinea pigs in PCB-induced alteration of serum thyroid hormone level
  • PCBルイ ニ ヨル コウジョウセン ホルモンカク ランサクヨウ ト ソノ サヨウ キコウ ドウブツ シュサ

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In the present study, we investigated the mechanism for the decrease in levels of serum thyroid hormones, especially thyroxine (T4) , by polychlorinated biphenyls (PCBs) such as Kanechlor-500 (KC500) , 2,2’,4’,5,5’-pentachlorobiphenyl (PentaCB) , and 2,2’,3’,4’,5,6-hexachlorobiphenyl (HexaCB) , and studied species differences among mice, hamsters, rats, and guinea pigs in the PCB effect. Significant decrease in serum total T4 level by KC500 was observed in all four species. On the other hand, there were differences in the level of decrease of serum total T4 level by PentaCB and HexaCB. Differences in the level of hepatic methylsulfonyl-PCB metabolites of KC500, PentaCB and HexaCB, which were thought to be associated with the PCB-toxic effects, did not necessarily correlate with the magnitude of decrease in serum total T4 level. Likewise, the induction of UDP-glucuronosyltransferases (T4-UDP-GT) toward T4 by PCB did not necessarily correlate with the decrease in serum T4 level in the animals used. Further studies on transthyretin (TTR) and serum T4-transporter suggested that decrease in serum total T4 level induced by PCB occurred not only by induction of T4-UDP-GT but also by the alteration of levels of T4-TTR binding and hepatic T4-transporter. In addition, species difference in the decrease of serum total T4 was associated with various PCB-induced total effects, including induction of T4-UDP-GT, decrease in T4-TTR binding level, the increase of hepatic thyroid hormone transporter, and other thyroid function correlates.

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