Rat liver microsomal UDP-glucuronosyltransferase activity toward thyroxine: characterization, induction, and form specificity

Toxicol Appl Pharmacol. 1992 Aug;115(2):261-7. doi: 10.1016/0041-008x(92)90331-l.


Glucuronidation of thyroxine (T4) by liver microsomal UDP-glucuronosyltransferase (UDP-GT) is a predominant pathway by which T4 is deactivated. This study was conducted to characterize in vitro T4 UDP-GT activity in rat liver microsomal preparations, to determine if T4 glucuronidation is mediated by a particular form of UDP-GT, and to determine if T4 glucuronidation can be increased by microsomal enzyme inducers. Characterization of microsomal T4 UDP-GT activity led to the establishment of optimal assay conditions. UDP-GT activity toward T4 was determined in hepatic microsomal preparations from Wistar and Gunn rats, a mutant strain of Wistar rats deficient in several forms of UDP-GT. Hepatic microsomal preparations from Gunn rats glucuronidated T4 at one-third the rate catalyzed by microsomal preparations from Wistar rats. To determine the effect of four inducers that each increase a separate class of UDP-GT, phenobarbital (PB), 3-methylcholanthrene (3MC), pregnenolone-16 alpha-carbonitrile (PCN), clofibrate (CLO), saline, or corn oil was administered to male Sprague-Dawley rats ip for 4 days. T4 UDP-GT activity was increased by PB, 3MC, PCN, and CLO 88, 150, 100, and 160%, respectively on a per-milligram-microsomal-protein basis and 138, 125, 100, and 145% on a per-kilogram-body-weight basis, respectively. Therefore, all four classes of UDP-GT inducers increase T4 glucuronidation, suggesting that T4 is not a selective substrate for a particular form of UDP-GT.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Enzyme Induction / drug effects
  • Glucuronates / analysis
  • Glucuronosyltransferase / metabolism*
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Male
  • Microsomes, Liver / enzymology*
  • Rats
  • Rats, Inbred Strains
  • Thyroxine / administration & dosage
  • Thyroxine / analogs & derivatives
  • Thyroxine / analysis
  • Thyroxine / metabolism*


  • Glucuronates
  • Iodine Radioisotopes
  • thyroxine glucuronide
  • Glucuronosyltransferase
  • Thyroxine