Hormones and Polyamines in Intestinal and Pancreatic Adaptation

Abstract

Dowling RH, Hosomi M, Stace NH, Lirussi F, Miazza B, Levan H, Murphy GM. Hormones and polyamines in intestinal and pancreatic adaptation. Scand J Gastroenterol 1985, 20(suppl 112), 84–95.

The evidence for and against an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, and exocrine pancreatic, strucutre and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. the trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of ‘enterotrophin’ while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. the cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO). When polyamine synthesis is blocked with the ODC inhibitor, difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreatico-biliary diversion is either inhibited or completely prevented. A proposed sequence of events might be as follows: luminal nutrients, particularly long-chain fats, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines, which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division, and adaptive tissue growth.

Key Words:

• Difluoromethyl ornithine
• exocrine pancreatic function
• enterotrophic hormones
• intestinal adaptation
• intestinal hyperplasia
• ornithine decarboxylase
• pancreatic adaptation
• pancreatic hyperplasia/hypertrophy
• pancreaticotrophic hormones
• polyamines