PT  - JOURNAL ARTICLE
AU  - Kato, Yoshihisa
AU  - Haraguchi, Koichi
AU  - Ito, Yuriko
AU  - Fujii, Aki
AU  - Yamazaki, Tomoaki
AU  - Endo, Tetsuya
AU  - Koga, Nobuyuki
AU  - Yamada, Shizuo
AU  - Degawa, Masakuni
TI  - Polychlorinated Biphenyl-Mediated Decrease in Serum Thyroxine Level in Rodents
AID  - 10.1124/dmd.109.031153
DP  - 2009 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.109.031153
4099  - http://dmd.aspetjournals.org/content/early/2009/12/29/dmd.109.031153.short
4100  - http://dmd.aspetjournals.org/content/early/2009/12/29/dmd.109.031153.full
AB  - Effects of Kanechlor-500 (KC500), a commercial polychlorinated biphenyl mixture, on the levels of serum thyroid hormones such as total thyroxine (T4) and triiodothyronine were examined in male mice, hamsters, rats and guinea pigs. Four days after a single intraperitoneal injection of KC500, significant decreases in the levels of the serum total T4 and free T4 occurred in all the animals examined, while a significant decrease in the level of serum triiodothyronine was observed only in guinea pigs among the animals examined. In addition, no significant change in the level of serum thyroid stimulating hormone was observed in any of the rodents examined. A significant increase in the activity of hepatic T4-UDP-glucuronosyltransferase after the KC500 administration occurred only in guinea pigs, while the increase in the amount of biliary [125I]T4-glucuronide after an intravenous injection of [125I]T4 to the KC500-pretreated animals occurred only in rats. On the other hand, in all the rodents examined, KC500-pretreatment promoted the clearance of [125I]T4 from the serum and led to a significant increase in the steady state distribution volumes of [125I]T4. Likewise, its pretreatment raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [125I]T4 in all the rodents tested. The present findings for the first time indicate that the KC500-mediated decrease in the serum T4 level in mice, hamsters, rats and guinea pigs occurs mainly through an increase in the accumulation level of T4 in the liver.The American Society for Pharmacology and Experimental Therapeutics