Epidermal growth factor-stimulated rabbit oesophageal mucosal growth: Role of polyamines

Factors operative in oesophageal mucosa growth are poorly characterized. Epidermal growth factor (EGF) has been shown to stimulate mucosal growth throughout the gastrointestinal tract. The present study was performed to test the hypothesis that polyamine biosynthesis is required for stimulation of epithelial growth by EGF in oesophageal mucosa. Using an in vitro explant model, oesophageal mucosal growth was quantified in the presence or absence of EGF and alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis. Administration of 50 nmol/L EGF significantly increased the rate of epithelial growth in oesophageal explants. Treatment with DFMO for 3 and 7 days not only depleted the tissue polyamines putrescine, spermidine and spermine, but also significantly impaired mucosal growth. The inhibitory effect of DFMO on mucosal growth was partially but significantly prevented when exogenous putrescine was given. Additionally, stimulation of epithelial growth by EGF was also blocked by depletion of cellular polyamines in DFMO-treated oesophageal explants. These results indicate that EGF stimulates epithelial growth of oesophageal mucosa at least partly through a process involving polyamine biosynthesis.