The biosynthesis and induction of microsomal UDP-glucuronyltransferase in avian liver.

Introduction The molecular mechanisms involved in the regulation of hepatic microsomal UDP-glucuronyltransferases are currently the subject of rigorous investigations by a number of laboratories. Overwhelming evidence indicates that UDPglucuronyltransferase is a heterogeneous family of enzymes (see Burchell, 1981); thus these investigations in mammalian tissues are complicated by the specificity and magnitude of measurable changes of transferase activities in response to inducing agents (Lillienblum et al., 1982). The developing chick embryo is in many respects a more convenient model for tackling some of the problems involved in the study of the control of gene expression by drugs and hormones (see Dutton, 1973; Grieninger & Granick, 1975). The activity of hepatic UDP-glucuronyltransferase towards various substrates is virtually absent from chickembryo liver until hatching, when it rises suddenly to adult values (Dutton & KO, 1966). Precocious development in ovo of this enzyme can be brought about by injection of phenobarbital or infusion of certain 11 8-hydroxy corticosteroids into embryonated eggs (Wishart & Dutton, 1975; Leakey et al., 1976), such that UDP-glucuronyltransferase activity is increased from virtually zero by some 50-fold by corticosterone acetate (Leakey et al., 1976) and up to 200fold by phenobarbital (Wishart & Dutton, 1975). These observations led to the discovery of the regulation of UDPglucuronyltransferase by glucocorticoids in developing mammalian liver (Wishart & Dutton, 1977). The enormous increases of UDP-glucuronyltransferase activity mediated by phenobarbital in chick-embryo liver in ouo can also be demonstrated in chick-embryo liver cultures (Burchell et al., 1972). Thus the developing chick-embryo liver cell provides an excellent model for study of the molecular mechanisms involved in regulation of UDP-glucuronyltransferase activity by drugs and hormones. We are currently investigating the transcriptional and translational events involved in drug-mediated stimulation of UDP-glucuronyltransferase synthesis in avian liver.