PT  - JOURNAL ARTICLE
AU  - Kato, Yoshihisa
AU  - Ikushiro, Shin-ichi
AU  - Takiguchi, Rie
AU  - Haraguchi, Koichi
AU  - Koga, Nobuyuki
AU  - Uchida, Shinya
AU  - Sakaki, Toshiyuki
AU  - Yamada, Shizuo
AU  - Kanno, Jun
AU  - Degawa, Masakuni
TI  - A Novel Mechanism for Polychlorinated Biphenyl-Induced Decrease in Serum Thyroxine Level in Rats
AID  - 10.1124/dmd.107.017327
DP  - 2007 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1949--1955
VI  - 35
IP  - 10
4099  - http://dmd.aspetjournals.org/content/35/10/1949.short
4100  - http://dmd.aspetjournals.org/content/35/10/1949.full
SO  - Drug Metab Dispos2007 Oct 01; 35
AB  - We have previously suggested that the decrease in the levels of serum total thyroxine (T4) and free T4 by a single administration to rats of Kanechlor-500 (KC500) at a dose of 100 mg/kg is not necessarily dependent on the increase in hepatic T4-UDP-glucuronosyltransferase (UDP-GT). In the present study, we determined whether or not a consecutive treatment with KC500 at a relatively low dose (10 mg/kg i.p., once daily for 10 days) results in a decrease in the level of serum total T4 and further investigated an exact mechanism for the KC500-induced decrease in the T4. At 4 days after final treatment with KC500, the serum total T4 and free T4 levels were markedly decreased in both Wistar and UGT1A-deficient Wistar (Gunn) rats, whereas significant increases in hepatic T4-UDP-GT activity were observed in Wistar rats but not in Gunn rats. The level of serum thyroid-stimulating hormone was not significantly changed in either Wistar or Gunn rats. Clearance from serum of the [125I]T4 administered to the KC500-pretreated Wistar and Gunn rats was faster than that to the corresponding control (KC500-untreated) rats. The accumulated level of [125I]T4 was increased in several tissues, especially the liver, in the KC500-pretreated rats. The present findings demonstrated that a consecutive treatment with KC500 resulted in a significant decrease in the level of serum total T4 in both Wistar and Gunn rats and further indicated that the KC500-induced decrease would occur through increase in accumulation of T4 in several tissues, especially the liver, rather than increase in hepatic T4-UDP-GT activity. The American Society for Pharmacology and Experimental Therapeutics