4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl-mediated decrease in serum thyroxine level in mice occurs through increase in accumulation of thyroxine in the liver.
4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl (4-OH-CB187) was selected as a major hydroxylated polychlorinated biphenyl metabolite detected from serum of wildlife and humans and was examined for its effect on level of serum thyroid hormone in mice. Four days after treatment of C57BL/6 and DBA/2 mice with 4-OH-CB187 (1.0 mg/kg), the serum total thyroxine (T(4)) and free T(4) levels were decreased in both strains of mice. On the other hand, no significant changes in the level and activity of the T(4)-UDP-glucuronosyltransferases, including UGT1a and UGT1a1, by the 4-OH-CB187 treatment were observed in either strain of mice. No 4-OH-CB187-mediated change in level of serum thyroid-stimulating hormone was observed in either strain of mice. Binding levels of [(125)I]T(4) to serum proteins after administration of [(125)I]T(4) were significantly changed in 4-OH-CB187-pretreated mice: a decrease in the level of serum [(125)I]T(4)-transthyretin (TTR) complex and an increase in the binding level of [(125)I]T(4) to serum albumin and thyroxine binding protein in both strains of mice. Clearance from serum of T(4) was promoted by 4-OH-CB187 pretreatment in both C57BL/6 and DBA/2 mice, and the levels of T(4) in several tissues, especially the liver, were increased. In addition, 4-OH-CB187-mediated decreases in serum total T(4) and free T(4) levels were observed in wild-type and TTR-heterozygous mice but not in TTR-deficient mice. The present findings show that 4-OH-CB187 shows a definite ability to decrease serum T(4) level and further indicate that the 4-OH-CB187-induced decrease would occur through increase in accumulation of T(4) in the liver.
Kato
Yoshihisa
Y
Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa 769-2193, Japan. kato@kph.bunri-u.ac.jp.
Haraguchi
Koichi
K
Kubota
Makiko
M
Seto
Yoshiki
Y
Ikushiro
Shin-ichi
S
Sakaki
Toshiyuki
T
Koga
Nobuyuki
N
Yamada
Shizuo
S
Degawa
Masakuni
M
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000097:blood* / Q000378:metabolism; D013974:Thyroxine / Q000097:blood* / Q000378:metabolism; D014018:Tissue Distribution
D001798:Blood Proteins; D013963:Thyroid Hormones; C034559:2,3,4,5,3',4',5'-heptachlorobiphenyl; D011078:Polychlorinated Biphenyls; D013974:Thyroxine