Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats.
Metabolism of thyroid hormones was investigated in WAG/MBL rats that had been exposed to hexachlorobenzene (HCB). Serum thyroxine (T4) levels were lowered by 35.5%, whereas triiodothyronine (T3) levels were not changed. Bile flow, as well as T4 excretion in bile were increased by HCB treatment. Analysis of bile by HPLC revealed a more than 3-fold increase of T4 glucuronide (T4G) and a concomitant reduction of non-conjugated T4. T4 UDP-glucuronyltransferase activity (T4 UDPGT) activity in hepatic microsomes was increased more than 4.5-fold in animals exposed to HCB. p-Nitrophenol (PNP) UDPGT showed a comparable increase by HCB. Both T3 and androsterone UDPGT activities were low in WAG/MBL rats compared with normal Wistar rats. T3 UDPGT activity was increased 2.5-fold by HCB, but androsterone UDPGT activity was unchanged. These results suggest that T4 is a substrate for HCB-inducible PNP UDPGT and T3 for androsterone UDPGT. In the absence of the latter, T3 is also glucuronidated to some extent by PNP UDPGT. Type 1 iodothyronine deiodinase activity was decreased by HCB treatment. It is concluded that decreased T4 levels in serum of animals after exposure to HCB may be due to a combined effect of displacement of T4 from carriers, an increased glucuronidation of T4 and enhanced bile flow.
van Raaij
J A
JA
Institute of Public Health and Social Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
Kaptein
E
E
Visser
T J
TJ
van den Berg
K J
KJ
D000738:Androsterone / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006581:Hexachlorobenzene / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D051381:Rats; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D005965:Glucuronates; D009596:Nitrophenols; D013963:Thyroid Hormones; D014284:Triiodothyronine; D006581:Hexachlorobenzene; D000738:Androsterone; D007453:Iodide Peroxidase; D014453:Glucuronosyltransferase; D013974:Thyroxine; C024836:4-nitrophenol