Expression of Hepatic Transforming Growth Factor Receptors During Late Gestation in the Fetal Rat*

Abstract

Transforming growth factor-alpha (TGF alpha) promotes DNA synthesis in adult rat hepatocytes, an effect opposed by picomolar concentrations of TGF beta. Recently, the presence of these growth factors in fetal rat liver has been demonstrated. Since a regulatory role for TGF alpha and TGF beta in fetal hepatic growth requires the presence of high affinity receptors, the receptors for these hormones were studied in membranes from normal fetuses at 17-21 days gestational age and growth-retarded fetuses of mothers fasted for 48 h. Fetal liver membranes bound [125I]epidermal growth factor ([125I]EGF) with high affinity (Kd = 1-2 nM). TGF alpha could compete with EGF for the same binding site, albeit at 4-fold lower affinity. EGF receptor number increased from nearly undetectable levels at 17 days to adult levels (0.15-0.3 nmol/mg membrane protein) by 21 days. Affinity labeling of fetal liver membranes with [125I]TGF alpha identified the 170,000 mol wt (Mr) EGF receptor. The intensity of labeling correlated with EGF receptor number based on binding analyses. TGF beta bound to fetal liver membranes with high affinity (Kd = 30 pM) and at a level (20-30 pmol/mg throughout late gestation) that was 3-fold higher than in adult liver. Affinity labeling of fetal hepatic membranes with [125I]TGF demonstrated high affinity 85,000 Mr TGF beta receptors and lower affinity 66,000 and 130,000 Mr receptors. Although TGF beta binding did not change with advancing gestation, affinity labeling of the 85,000 Mr protein doubled from day 18 to day 21 and was decreased by 50% in fetuses from fasted mothers. These data, demonstrating the presence and regulation of the receptors for TGF alpha and TGF beta, support roles for these hormones in the regulation of fetal hepatic growth.