Epidermal growth factor in protection, repair, and healing of gastroduodenal mucosa

Gastrointestinal mucosa is one of the most rapidly proliferating tissues in the body and the alteration in the balance between cell regeneration and cell loss may lead to mucosal lesions and ulcerations. Mucosal growth is under the influence of various growth factors, among which epidermal growth factor (EGF) and polyamines seem to play a crucial role. EGF is produced in large quantities in salivary and pancreatic glands and secreted mainly into the gut lumen and partly released into the bloodstream from where it is cleared by the kidneys and excreted into the urine as urogastrone. The physiological role of EGF is still under active investigations but it appears that EGF may be required for the maintenance of mucosal integrity and healing of mucosal defects due to its accumulation in the lesion area and local stimulation of healing processes. The mechanism of protective and ulcer healing effects of EGF involves the activation of ornithine decarboxylase (ODC), the key enzyme in the biosynthesis of polyamines, which play a crucial role in the growth-promoting action of EGF. Substances that affect the generation and/or catabolism of polyamines affect the gastroprotective and ulcer healing effect of EGF but not that of exogenous polyamines. Mucosal generation of protective prostaglandins appears to be essential mainly for the gastro-protective effects of EGF but seem to be of little importance in the healing effects of EGF on acute and chronic gastroduodenal ulcerations.