The effect of dexamethasone and glucagon on the expression of hepatocyte plasma membrane proteins during development

Abstract

The regulation of different maturational processes in the liver is believed to be influenced by the hormonal system. The aim of this study was to investigate the effect of two hormones, glucagon and dexamethasone, on levels of plasma membrane proteins in rat liver cells during late fetal and early postnatal stages of development. For this purpose, 18-day-old rat fetuses and 1-day-old newborns were treated with glucagon or dexamethasone and killed at 22 days of gestation and 3, 5 and 7 days of age, respectively. Postnuclei liver membranes were isolated using a sucrose gradient method and assessed for levels of specific membrane proteins. Asialoglycoprotein receptor and 110,000 Mr glycoprotein, denoted GP 110, representing the sinusoidal and bile canalicular domains, respectively, were quantitated using the immunoblot method. Membrane enzymes alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transferase were evaluated using enzymatic methods. The data showed that glucagon and dexamethasone have a differential effect on membrane constituents according to the stage of development. Glucagon increased the levels of membrane enzymes during the late fetal stage but had no effect on liver membrane proteins in the newborn animal. In contrast, although dexamethasone elevated GP 110 in fetal rat livers, none of the other marker proteins was significantly affected. On the other hand, in newborns dexamethasone reduced the amount of asialoglycoprotein receptor and alkaline phosphatase and leucine aminopeptidase enzyme activities but greatly augmented the level of gamma-glutamyl transferase. Thus, glucagon primarily affects plasma membrane proteins in late gestation while dexamethasone does so during the early postnatal period. The roles that these two hormones may play during ontogeny is discussed with respect to liver development.