Regulation of gastrointestinal mucosal growth

Abstract

The regulation of the growth of gastrointestinal tract mucosa is unique and, compared with most other tissues in the body, complex. Mucosal growth is affected by the same hormones (insulin, growth hormone, thyroxine, cortisol) that alter metabolism in other tissues, but the gastrointestinal mucosa also responds to a host of events triggered by the ingestion and presence of food within the digestive tract. Food results in the release of several gasrointestinal hormones that specifically affect only tissues of the digestive tract. These hormones have been shown to regulate the growth of the exocrine pancreas, gallbladder, epithelium, and the mucosa of the oxyntic gland region of the stomach and the small and large intestines. Less well defined than the gastrointestinal peptides are various factors theorized to affect the mucosa from within the lumen. These include secretions (especially those of the pancreas and liver), so-called luminal nutrition, and additional dietary constituents that stimulate growth independent of their nutritive value. These factors remain mostly hypothetical, since their physiological significance has not been proven rigorously. The common property of these stimulants, which accounts for their scientific interest, is that they occur within the lumen, distributed over a proximal-to-distal gradient. Because nutrients or other dietary factors and secretions are diluted, absorbed, and destroyed as they pass down the tract, their effects on the mucosa would also decrease distally. Such a mechanism therefore could explain the villous-height-crypt-depth gradient and a variety of adaptations that follow altered exposure of portions of the gut to luminal contents. In this review the author examined the trophic properties of a variety of gastrointestinal peptides and some of the hypotheses invoked to explain the gradient-oriented nature of mucosal growth. To summarize part of the knowledge in this area, the author reviews the role of polyamines in mucosal growth and presents a totally theoretical model that, if not correct, at least explains many observations.