Trophic Effects of Gut Hormones in the Gastrointestinal Tract

This chapter focuses on the effects of gastrointestinal (GI) hormones on the proliferation and repair of non-neoplastic tissues, and the receptors and signaling pathways, which transmit signals from the cell surface to the nucleus. Gastrin is the GI hormone that stimulates acid secretion from gastric parietal cells, and is the single most important trophic hormone for the gastric mucosa. One of the peptides that stimulates gastric mucosal proliferation is bombesin (BBS)/gastrin-releasing peptide (GRP), which stimulates pancreatic, gastric, and intestinal secretion, gut motility, and smooth muscle contraction, and release of all gut hormones. These peptides can stimulate growth of GI mucosa and pancreas. BBS also stimulates growth of the small bowel mucosa. Administration of BBS effectively prevented mucosal atrophy associated with feeding rats a liquid elemental diet. GI hormone-stimulated signal transduction occurs with the binding of hormones to their cognate cell surface receptors, which are G-protein-coupled receptors (GPCR). These receptors have the typical structural features of G-protein-binding seven-transmembrane receptors, which are G-protein-coupled receptors (GPCR). These receptors have the typical structural features of G-protein-binding seven-transmembrane receptors which can regulate a number of physiological processes, including proliferation, growth, and development. The molecular mechanisms though which GPCRs transduce signals are complex, and likely involve multiple signaling pathways. In addition, the signaling pathways are likely cell-specific, which may explain the diverse physiologic functions controlled by gut hormones, ranging from regulation of secretion, motility, and in some instances growth, depending on the target tissue. Once a trophic GI peptide binds its seven-transmembrane GPCR, signal transduction pathways are activated which ultimately can lead to cell proliferation depending upon cell type.