Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats

Biochem Pharmacol. 1993 Feb 9;45(3):627-31. doi: 10.1016/0006-2952(93)90136-k.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androsterone / metabolism
  • Animals
  • Bile / metabolism
  • Glucuronates / metabolism*
  • Glucuronosyltransferase / metabolism
  • Hexachlorobenzene / pharmacology*
  • Iodide Peroxidase / metabolism
  • Male
  • Microsomes, Liver / metabolism
  • Nitrophenols / metabolism
  • Rats
  • Thyroid Hormones / metabolism*
  • Thyroxine / blood
  • Thyroxine / metabolism
  • Triiodothyronine / metabolism

Substances

  • Glucuronates
  • Nitrophenols
  • Thyroid Hormones
  • Triiodothyronine
  • Hexachlorobenzene
  • Androsterone
  • Iodide Peroxidase
  • Glucuronosyltransferase
  • Thyroxine
  • 4-nitrophenol