Chronic administration of epidermal growth factor to pigs induces growth, especially of the urinary tract with accumulation of epithelial glycoconjugates.

BACKGROUND

Epidermal growth factor (EGF) receptor hyperstimulation induced by systemically administered EGF or by the development of transgenic mice overexpressing transforming growth factor alpha (TGF alpha) or other EGF-related ligands is known to induce various effects, such as acceleration of developmental processes like incisor eruption, inhibition of gastric acid secretion, morphologic changes in the pancreas resembling pancreatitis, and malignancies in mammary glands and the liver. The present investigation was initiated to explore the effects of systemic EGF administration to the mature organism in a species with greater anatomic resemblance to humans than rodents.

EXPERIMENTAL DESIGN

Eleven Goettingen Minipigs underwent 4 weeks of treatment either with placebo (n = 5) or human recombinant EGF 30 micrograms/kg/day (n = 6) administered subcutaneously. At the end of Week 4, the animals were sacrificed, autopsy was performed, and tissue samples were collected for histologic examination.

RESULTS

EGF treatment caused macroscopic enlargement of the ureters, kidney, and heart. The ureters increased 4-fold in cross sectional area due to growth of all wall layers. The urothelium was hyperplastic with intracellular accumulations of material staining with Periodic acid-Schiff. Similar but less pronounced changes were found in the pancreas, lungs, salivary glands and esophagus.

CONCLUSIONS

The most important observation of the present study is that systemic treatment with EGF for 4 weeks induces considerable growth to the urinary tract. We suggest new biologic effects of the EGF family in promoting growth of the urinary tract and in stimulating epithelial glycoconjugate biosynthesis in the urothelium and excretory ducts of the pancreas.