Species differences among mice, hamsters, rats and guinea pigs in PCB-induced alteration of serum thyroid hormone level

在本研究中，我们探讨了多氯联苯降低血清甲状腺激素水平，特别是甲状腺激素(T_4)水平的机制，并研究了多氯联苯对小鼠、仓鼠、大鼠和豚鼠的影响。KC500能显著降低四种动物的血清总T_4水平。而血清总T_4水平的降低程度在五氯联苯和六氯联苯中存在差异。被认为与多氯联苯毒性作用有关的KC500、五氯二苯和六氯联苯的肝脏甲磺酰基多氯联苯和羟基多氯联苯代谢物水平的差异，与血清总T_4水平下降的幅度并不一定相关。同样，多氯联苯对T_4的诱导也不需要…。更多的是与所用动物血清T_4水平的下降有关。此外，PCb介导的UGT1a缺陷Wistar大鼠(Gunn大鼠)血清总T_4水平下降，而肝脏T_4-UDP-GT活性未见升高。对转甲状腺素和血清T_4转运蛋白的进一步研究表明，多氯联苯不仅通过诱导T_4-UDP-GT降低血清总T_4水平，而且还通过改变T_4-TTR结合水平和肝脏T_4转运蛋白水平来降低血清总T_4水平。此外，血清总T_4水平下降的物种差异与多氯联苯诱导的各种总效应有关，包括诱导T_4-UDP-GT、降低T_4-TTR结合水平、增加肝脏甲状腺激素转运体，以及其他甲状腺功能相关。综上所述，本研究结果表明，在所使用的动物中，多氯联苯引起的血清T_4水平的下降不仅仅是通过肝脏T_4-UDP-GT的增加来实现的，而且进一步表明，在所有四种动物中，多氯联苯介导的下降都是通过增加T_4向肝脏的转运而发生的。此外，T_4与血清TTR结合力的降低和肝组织的增生可能与肝脏T_4水平升高有关。为了了解包括人类在内的动物对多氯联苯引起的血清T_4水平下降的易感性，有必要进行进一步的研究。较少

In the present study, we investigated the mechanism for the decrease in levels of serum thyroid hormones, especially thyroxine (T_4), 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 difference among mice, hamsters, rats, and guinea pigs in the PCB effect. Significant decrease in serum total T_4 level by KC500 was observed in all four species. On the other hand, there were differences in the level of decrease of serum total T_4 level by PentaCB and HexaCB. Differences in the level of hepatic methylsulfonyl-PCB and OH-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 T_4 level. Likewise, the induction of CYP1A, CYP2B, CYP3A, iodothyronine deiodinase and UDP-glucuronosyltransferases (T_4-UDP-GT) toward T_4 by PCB did not necess … More arily correlate with the decrease in serum T_4 level in the animals used. In addition, the PCB-mediated decrease in serum total T_4 level in UGT1A-deficient Wistar rats (Gunn rats) occurred without an increase in hepatic T_4-UDP-GT activity. Further studies on transthyretin (TTR) and serum T_4-transpoter suggested that decrease in serum total T_4 level by PCB occurred not only by induction of T_4-UDP-GT but also by the alteration of levels of T_4-TTR binding and hepatic T_4-transporter. In addition, species difference in the decrease of serum total T_4 level was associated with various PCB-induced total effects, including induction of T_4-UDP-GT, decrease in T_4-TTR binding level, the increase of hepatic thyroid hormone transporter, and other thyroid function correlates. In conclusion, the present findings suggest that in the animals used, the PCB-induced decrease in serum T_4 level dose not occur only through increase in hepatic T_4-UDP-GT, and further suggest that in all four species, the PCB-mediated decrease occurs through the increased transportation of T_4 to the liver. Furthermore, the decrease in the binding of T_4 to serum TTR and hepatic hyperplasia might be attributed to the increase in the level of T_4 in the liver. Further studies are necessary for understanding the susceptibility toward a PCB-mediated decrease in serum T_4 level in animals including humans. Less