Expression of transforming growth factor-alpha and its receptor during human liver development and maturation.

We investigated the expression of transforming growth factor-alpha (TGF-alpha) and its receptor during human liver development and maturation, using immunohistochemistry. In the fetal liver, strong immunoreactivity for TGF-alpha and its receptor was noted in intrahepatic bile duct cells of various developmental stages; moderate immunoreactivity for TGF-alpha and mild immunoreactivity for TGF-alpha receptor were found in immature hepatocytes. In the postnatal liver, reactivity for TGF-alpha in hepatocytes decreased gradually and was negative or only weakly positive in the adult liver, while reactivity for TGF-alpha receptor in hepatocytes increased gradually and was strongly positive in the adult liver. In contrast, immunoreactivity of TGF-alpha and its receptor in intrahepatic bile duct cells persisted in the postnatal liver and was positive in the adult liver. These data suggest that the system of TGF-alpha and its receptor has an important role in the proliferation and differentiation of intrahepatic biliary cells and hepatocytes in the fetal liver. The decreasing expression of TGF-alpha in hepatocytes in the postnatal liver may indicate that proliferative activity of hepatocytes gradually decreases with liver maturation. The presence of TGF-alpha and its receptor in intrahepatic bile ducts in the postnatal liver suggests that the system of TGF-alpha and TGF-alpha receptor is operative postnatally.