Stimulation of rat oxyntic gland mucosal growth by epidermal growth factor

Abstract

Epidermal growth factor (EGF) inhibits gastric acid secretion, but its effects on the growth of gut mucosa have not been examined. Fasted male rats were given six injections of EGF (10 micrograms/kg) over a 48-h period. The animals were killed and the incorporation of [3H]thymidine into various tissues was examined and compared to rats treated with NaCl, pentagastrin, and EGF plus secretin. EGF and pentagastrin significantly increased DNA synthesis of the oxyntic gland mucosa. Pentagastrin, but not EGF, stimulated DNA synthesis of duodenal and colonic mucosa as well. Neither peptide altered skin DNA synthesis. Secretin inhibited the effects of pentagastrin but not EGF. Chronic administration of EGF (5 days) caused significant increases in oxyntic gland mucosal DNA, RNA, and protein content. These results not only demonstrate that EGF is a trophic agent for the oxyntic gland mucosa but lend further support to the hypothesis that acid secretion and mitogenesis are the result of two separate mechanisms.

Effect of sialoadenectomy and salivary gland extracts on gastrointestinal mucosal growth and gastrin levels in the rat.

“…Another likely mechanism through which the salivary glands might affect gastric mucosal growth is via the endogenous trophic substance, EGF (Feldman et al 1978; Johnson & Guthrie, 1980). Administration of a culture-grade preparation of EGF resulted in an increase in DNA synthesis in the oxyntic mucosa of sialoadenectomized rats.…”

“…Changes in the growth of either duodenal or colonic mucosa were inconsistent. Whereas pentagastrin has been shown to influence growth throughout the gastrointestinal tract (Johnson, 1976) there is some doubt as to whether EGF has the same widespread stimulatory capabilities for the gut (Chabot & Hugon, 1980;Johnson & Guthrie, 1980;Malo & Menard, 1982). Nevertheless, the inability of elimination of salivary tissue or administration of some trophic substances in the present study to alter growth in the small intestine or colon, as has been shown in previous studies (Johnson, 1976), may reflect a situation unique to the sialoadenectomized rat.…”

“…Injections followed the same regimen as described above for tissue extracts. The doses of EGF and pentagastrin had previously been shown to stimulate growth in rat gastric mucosa (Johnson & Guthrie, 1980). lastrin determinations in plasma and antral tissue.…”

“…Exogenous administration of epidermal growth factor (EGF), a polypeptide extracted from rodent salivary glands, has been shown to produce keratinization of gastric mucosa, with a thicker cellular nucleated epithelial layer and an increase in the mitotic index in neonatal mouse forestomach tissue (Cohen & Elliot, 1963;Steidler & Houghton, 1980). Studies by Feldman, Aures & Grossman (1978) and Johnson & Guthrie (1980) demonstrated that exogenous administration of EGF stimulated ornithine decarboxylase activity, and increased the content of DNA and RNA and the rate of DNA synthesis in rat oxyntic mucosa. EGF also appears to stimulate DNA synthesis or mitosis in rodent intestinal mucosa (Al-Nafussi & Wright, 1982;Chabot & Hugon, 1980).…”

Use of in vivo Whole-Body Autoradiography to Identify the Distribution of Epidermal Growth Factor Binding Sites under Normal Conditions in the Mouse Digestive System.

“…EGF has been detected in gastric juice (56), and it displays many biologic effects, including inhibition of gastric acid secretion (23,29,57), protection of the gastroduodenal mucosa (53), stimulation of proliferation and differentiation of the epithelium (46), and stimulation of mucin (87) and prostaglandin E production (18). Elder et al, suggested that EGF acts at the parietal cell in the epithelium of the stomach (29), and Forgue-Lafitte et al demonstrated biochemically that there was high 1251 binding in gastric glands isolated from antral and fundic parts of the guinea pig stomach (34).…”