THE EFFECT OF MATERNAL PROTED MALNUTRITION AND ETHANOL EXPOSURE ON EGF BINDING TO NEONATAL RAT HEPATOCYTES

Abstract

Epidermal Growth Factor (EGF) plays an important role in hepatocellular maturation and regeneration. We have shown that foetal and neonatal rat hepatocytes have fewer EGF receptors with reduced affinity for ligand compared to adult cells suggesting down-regulation of this receptor in developing cells. In order to evaluate the effect of maternal malnutrition and chronic ethanol exposure on EGF binding to neonatal hepatocytes female Sprague-Dawley rats were fed 1 of 3 diets two weeks prior to breeding until after parturition: 1) Rat chow (23% protein) with water ad lib (C), 2) liquid Lieber-Decarli diet with 10% protein (LP), and 3) the LP diet with 36% of maltose-dextrin calories replaced by ethanol (ELP). Isolated hepatocytes were prepared from 6 day old neonatal livers by collagenase digestion of minced livers. Binding was assessed by incubating cells at 37 C with varying concentraticns of 125I-EGF (0.16 nM-7.8 nM) for 60 minutes. There was an increase in both the number of surface receptors (B_max (x 10 ⁴/cell, mean +/- SEM n=3:) - C = 1.78 +/- 0.35; LP = 2.35 +/- 0.56 p=NS; ELP = 3.53 +/- 0.55; P<0.02.) and the binding affinity for EGF (K_d × 10⁻¹⁰M C = 6.54 +/- 0.34; LP = 5.17 +/- 1.12 p = NS; ELP = 4.69 +/- 0.7 p<0.02) in hepatocytes from both treated groups compared to controls although this was only significant in group ELP.

It is concluded that the combination of maternal protein malnutrition and ethanol exposure in utero alters the regulation of EGF processing in developing hepatocytes which may retard hepatocellular maturation and development.

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