Abstract

Antibodies directed against three isozymes of rat hepatic microsomal UDP-glucuronosyltransferase (EC 2.4.1.17), p-nitrophenol, 3 alpha-hydroxysteroid, and 17 beta-hydroxysteroid UDP-glucuronosyltransferases were used to localize these enzymes at the light microscopic level in livers of untreated Sprague-Dawley and Wistar rats. Avidin-biotin-peroxidase staining revealed the presence of each isozyme within parenchymal cells throughout the liver lobule in rats of both strains. However, although antibodies to the 3 alpha- and 17 beta-hydroxysteroid UDP-glucuronosyltransferases appeared to stain hepatocytes across the liver lobule quite uniformly, centrilobular hepatocytes were stained much more intensely for p-nitrophenol UDP-glucuronosyltransferase than were midzonal and periportal cells. Additionally, appreciable immunohistochemical staining for p-nitrophenol UDP-glucuronosyltransferase, but not for the two hydroxysteroid UDP-glucuronosyltransferases, was detected within the epithelium of the hepatic bile duct and the endothelium of the hepatic artery and portal vein. Another difference was noted in livers of Wistar rats: hepatocytes of rats possessing low 3 alpha-hydroxysteroid (i.e., androsterone) UDP-glucuronosyltransferase activity were stained much less intensely for the 3 alpha-hydroxysteroid UDP-glucuronosyltransferase than were those of rats exhibiting high rates of androsterone glucuronidation, whereas differences in immunoperoxidase staining for p-nitrophenol and 17 beta-hydroxysteroid UDP-glucuronosyltransferases were not apparent between the two subclasses of Wistar rats. These immunohistochemical findings demonstrate that different UDP-glucuronosyltransferase isozymes are distributed across the liver lobule in significantly different manners and, furthermore, suggest that xenobiotics may be glucuronidated within epithelial cells of the hepatic bile duct and endothelial cells of the hepatic artery and portal vein, as well as within hepatocytes. The results of this study also provide evidence that differences in the content of 3 alpha-hydroxysteroid UDP-glucuronosyltransferase within hepatocytes account for genetically determined variations in the rates at which androsterone and certain other xenobiotics are glucuronidated in livers of Wistar rats.