INHIBITION OF BILIRUBIN CONJUGATION IN RAT LIVER SLICES BY HUMAN PREGNANCY AND NEONATAL SERUM AND STEROIDS

Abstract

Rat liver slices conjugated bilirubin with glucuronic acid in the presence of rat sera or human sera.Sera from pregnant women and newborn infants inhibited the conjugation.Conjugation in liver slices from rabbits and monkeys was inhibited to a smaller extent.The inhibitor was heat-stable and dialyzed slowly.Conjugation in rat (but not rabbit and monkey) liver slices was inhibited by a number of steroids.Neither sera nor steroids affected the rate of conjugation of o-aminophenol in liver slices or the conjugation of bilirubin by broken cell preparations of liver.The inhibitory activity of sera from newborn infants with non-haemolytic jaundice was the same as that of infants who were not jaundiced.It is probable that the inhibitor makes only a minor contribution to the development of jaundice in the newborn infant.Sera from several domestic animals also inhibited conjugation of bilirubin in rat liver slices.BILIRUBIN is conjugated with glucuronic acid by liver slices [Lathe and Walker, 1957 and 1958 b] and suspensions [Grodsky and Carbone, 1957;Schmid, Hammaker and Axelrod, 1957].We obtained higher rates of conjugation by rat liver slices when serum was incorporated in the incubation medium: the serum protein probably serves to retain the bilirubin in solution.It was observed that the use of human pregnancy and neonatal sera and certain animal sera reduced the rate of conjugation below that obtained with rat serum or pooled human male serum.These inhibitory effects, some of which were reproduced with steroids, have been discussed in a preliminary report [Lathe and Walker, 1958 a].