GLUCURONIDATION AND DEGLUCURONIDATION REACTIONS IN HEPATIC AND EXTRAHEPATIC TISSUES DURING PERINATAL DEVELOPMENT

Abstract

The relative activities of uridine diphosphoglucuronyltransferase (UDPGT) and .beta.-glucuronidase (.beta.G) were measured during perinatal development of hepatic and extrahepatic tissues to determine the balance between glucuronidation and deglucuronidation reactions at different developmental stages. Liver, lung, kidney, intestine and placenta were studied in guinea pigs and rabbits. In general, .beta.G activities exceeded those of UDPGT in fetal tissues, whereas the converse was evident in adults. There were significant species and age differences in the onset of .beta.G and UDPGT activities and the occurrence of developmental peaks. A dramatic .beta.G developmental peak was observed in fetal guinea pig intestine and newborn rabbit intestine. Both microsomal and lysosomal .beta.G exhibited similar developmental patterns in all tissues tested. Hepatic nonsteroid UDPGT activities were higher at parturition than in adult animals, whereas no such developmental peak occurred for steroid UDPGT. Triton X-100 activated fetal UDPGT in vitro by approximately the same factor as it did for adult UDPGT. [Considerable attention has been focused recently on the role that extrahepatic drug metabolism plays in the disposition and eventual toxicity of xenobiotics].