Epidermal growth factor-stimulated rabbit oesophageal mucosal growth: Roleof polyamines

Factors operative in oesophageal mucosa growth are poorly characterized. Ep idermal growth factor (EGF) has been shown to stimulate mucosal growth thro ughout the gastrointestinal tract. The present study was performed to test the hypothesis that polyamine biosynthesis is required for stimulation of e pithelial growth by EGF in oesophageal mucosa. Using an in vitro explant mo del, oesophageal mucosal growth was quantified in the presence or absence o f EGF and alpha-difluoromethylornithine (DFMO), a specific inhibitor of pol yamine synthesis. Administration of 50 nmol/L EGF significantly increased t he rate of epithelial growth in oesophageal explants. Treatment with DFMO f or 3 and 7 days not only depleted the tissue polyamines putrescine, spermid ine and spermine, but also significantly impaired mucosal growth. The inhib itory effect of DFMO on mucosal growth was partially but significantly prev ented when exogenous putrescine was given. Additionally, stimulation of epi thelial growth by EGF was also blocked by depletion of cellular polyamines in DFMO-treated oesophageal explants. These results indicate that EGF stimu lates epithelial growth of oesophageal mucosa at least partly through a pro cess involving polyamine biosynthesis.