Effects of polychlorinated biphenyls, kanechlor-500, on serum thyroid hormone levels in rats and mice.
Effects of a commercial polychlorinated biphenyls mixture, Kanechlor-500 (KC500), on the levels of serum thyroid hormones such as total thyroxine (T4) and triiodothyronine (T3) were examined comparatively in male Wistar rats and ddy mice. Serum T4 levels were significantly decreased in both rats and mice 4 days after a single ip injection of KC500 (100 mg/kg body weight), whereas decreased levels of T3 were observed in mice but not in rats. In addition, no significant change in the level of serum thyroid stimulating hormone was observed in either rats or mice. Hepatic UDP-glucuronosyltransferases (UDP-GTs) UGT1A1 and UGT1A6, which efficiently mediate glucuronidation of T4 and promote the excretion of the hormones, were induced by KC500 in rats but not in mice. Hepatic microsomal cytochrome P450 (P450) content and the microsomal activity for 7-ethoxy-, 7-pentoxy-, and 7-benzoyloxy-resorufin dealkylations were significantly increased by KC500 in both rats and mice, although the magnitude of increase in the enzyme activities was higher in rats than in mice. The difference in the increase in the activity of microsomal enzymes, including UDP-GT and P450, between KC500-treated rats and mice was not correlated with that in the level of hepatic methylsulfonyl-PCB metabolites. In the present study, we found for the first time that the decrease in serum T4 levels by KC-500 in mice occurred without increase in hepatic UDP-GTs, UGT1A1 and UGT1A6, responsible for T4 glucuronidation. The present findings further suggested that although the decrease in serum T4 levels in KC500-treated rats would occur at least in part through the induction of the UDP-GTs, it might not be dependent on only the increase in the enzymes.
Kato
Yoshihisa
Y
School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan. kato@ys7.u-shizuoka-ken.ac.jp
Haraguchi
Koichi
K
Yamazaki
Tomoaki
T
Ito
Yuriko
Y
Miyajima
Shoji
S
Nemoto
Kiyomitsu
K
Koga
Nobuyuki
N
Kimura
Ryohei
R
Degawa
Masakuni
M
D000818:Animals; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
C477388:KC 500; D012333:RNA, Messenger; D014284:Triiodothyronine; D013972:Thyrotropin; D011078:Polychlorinated Biphenyls; D014453:Glucuronosyltransferase; D013974:Thyroxine