Polyamines in the Regulation of Gastrointestinal Growth

Seidel, Edward

Abstract

The presence of food in the gut produces both direct and indirect effects on the growth of the gastrointestinal mucosa. Becasue ingestion of foodstuffs leads to increased desquamation of the epithelium and changes in luminal or local nutrition, direct effects on growth are produced when food moves through the gut after a meal. Indirect effects of a meal include release of GI hormones, increased secretions and increased activity of the autonomic nervous system. There may be a common mechanism which mediates both types of stimulation. The polyamines are a group of ubiquitously distributed polycations which are required for normal cell growth and proliferation. Preliminary studies have shown that they are involved in the regulation of mucosal growth. These data demonstrate that 1) there is a proximal to distal gut gradient of polyamine metabolism, 2) the aliphatic amine, ethylamine, has direct trophic effects in the gut, 3) the trophic response to intestinal obstruction has, as a required event, the induction of polyamine metabolism. These observation may explain 1) the proximal to distal gut gradient of villus height and crypt depth, 2) the role of amines, both aliphatic and polyamines, as regulators of GI mucosal growth, 3) the mechanism whereby the hormones of the gut exert their trophic in GI tissues, and 4) the as yet unexplained adaptive response of the gut to intestinal surgery. It is proposed to study and define the role of amines as regulators of mucosal growth. Initial experiments are designed to localize the areas of the gut in which amine metabolism is important to growth. It will also be necessary to study amine metabolism in the bacteria of the intestinal microflora as amines secreted from these cells may have direct effects on mucosal growth. It will be determined whether the hormones of the GI tract induce polyamine metabolism and whether this step is required for expression of their trophic effects. Finally, the role of amines as mediators of the adaptive response to intestinal surgery will be defined in various animal models of postsurgical hyperplasia and hypertrophy. The importance of a thorough understanding of GI growth is underscored by the realization that many diseases of the bowel, e.g., Zollinger-Ellison syndrome, chronic gastritis, pernicious anemia and the growth of cancers of the alimentary canal, are accompanied by disorders of gastrointestinal growth.