Chronic Systemic Treatment with Epidermal Growth Factor Induces Hypergastrinaemia in Goettingen Minipigs

Abstract

Background: Epidermal growth factor (EGF) is an inhibitor of gastric acid secretion. The impact of chronic systemic treatment with EGF on intragastric pH and serum gastrin concentrations has not been investigated previously. Methods: Goettingen minipigs were treated with human recombinant EGF (hEGF) or placebo for 4 weeks. Once a week the acidity and protein concentration of gastric juice were determined, and serum gastrin concentrations measured. After 4 weeks tissue specimens were obtained from the gastric antrum and immunostained for gastrin- and somatostatin-producing G- and D-cells. Furthermore, the development of antibodies against hEGF was evaluated. Results and Conclusion: Subcutaneously administered hEGF, 30 μg/kg/day for 4 weeks, included a fourfold increase in basal serum gastrin concentration, increased the number of antral G-cells, and decreased the density of antral D-cells. The acidity of gastric fluid was reduced, and the protein concentration increased. All animals developed low-titred antibodies towards hEGF. The antibodies did not influence the extent to which the individual animal responded to the EGF treatment.

Key Words:

• Immunohistochemistry
• pigs
• somatostatin
• transforming growth factor alpha