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

Section of Biochemistry, Brown University, and the Department of Pediatrics, Rhode Island Hospital, Providence Rhode Island 02903

Address requests for reprints to: Dr. Philip Gruppuso, Division of Pediatric Endocrinology and Metabolism, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02903.

Abstract

Transforming growth factor- (TGF) promotes DNA synthesis in adult rat hepatocytes, an effect opposed by picomolar concentrations of TGFβ. Recently, the presence of these growth factors in fetal rat liver has been demonstrated. Since a regulatory role for TGF and TGFβ 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 (K_d = 1–2 nM). TGF 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]TGFa identified the 170,000 mol wt (M_r) EGF receptor. The intensity of labeling correlated with EGF receptor number based on binding analyses. TGF/3 bound to fetal liver membranes with high affinity (K_d = 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 M_r TGF/3 receptors and lower affinity 66,000 and 130,000 M_r receptors. Although TGF/3 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 and TGFβ, support roles for these hormones in the regulation of fetal hepatic growth.

Footnotes

^* This work was supported by NIH Grant HD-24455.

Received April 17, 1989.