DIFFERENTIAL EXPRESSION OF THE NEUROTENSIN GENE IN THE DEVELOPING RAT AND HUMAN GASTROINTESTINAL-TRACT

Neurotensin (NT) is an important hormone regulating gut motility, secretion, and growth. The purpose of this study was to determine the developmental expression of the NT/neuromedin N gene (NT/N) in the gut and pancreas of rats and humans. We found that NT/N expression, initially low in the fetal rat jejunum and ileum, is increased by postnatal day 3. This increase is independent of contact with luminal nutrients as demonstrated by elevated NT/N expression in rat jejunoileal grafts implanted in nude mice. NT/N expression reaches maximal levels in the small bowel by postnatal day 14. After postnatal day 28, NT/N mRNA levels remain constant in the ileum but decrease in the jejunum. Transient NT/N expression is found in the colon of fetal and postnatal rats. Similar to the rat, NT/N expression is low in the human fetal ileum but increases in the adult. In the human colon, NT/N is transiently expressed in the fetus at midgestation but disappears by birth and, similarly, is not apparent in the adult. We conclude the following. 1) The NT/N gene demonstrates a complex pattern of tissue-specific expression; the jejunum and ileum show a similar pattern of expression until the end of the fourth postnatal week, when NT/N levels decrease in the jejunum to assume the distinctive adult topographical distribution with NT/N increasing along the jejunoileal axis. 2) NT/N is transiently expressed in the colon of rats and humans during a developmental stage characterized by morphological and functional similarities to the small bowel; therefore, NT/N may provide a useful endocrine marker to further define the complex differentiation pathway leading to small bowel and colonic phenotypes.