Precocious development of UDP-glucuronyltransferase activity in cultured fetal rat liver brought about by glucocorticoids and requiring amino acid incorporation into protein

Abstract

Fetal-rat liver explants cultured in a defined protein-free medium containing dexamethasone, corticosterone or cortisol (all 2 microM) exhibit precocious development of UDPglucuronyltransferase activity to o-aminophenol. Transferase activity in 14-day fetal livers cultured with the glucocorticoids for 3 days rises from virtually zero to 5 times the activity seen in fresh 17 day fetal liver. With 15-day fetal livers, precocity was also observed, but to a lesser degree. Precocity always required addition of glucocorticoids, though explants were viable without them. Protein synthesis, not activation, was probably involved, for assays were performed in a range of digitonin concentrations to ensure 'optimal' activation; also, precocious development of transferase activity and uptake of [14C]-leucine into protein exhibited parallel behaviour during inhibition by, and recovery from, cycloheximide-pulsing. This is the first demonstration of a protein-synthesis-dependent stimulation of fetal mammalian UDPglucuronyltransferase by known compounds of endogenous origin. Results with other substrates are discussed.