| The small intestine of domestic animals and humans develops relatively early in gestation compared to the rodent, suggesting that it may play a role in fetal development. In most neonatal animals, the small intestine is the primary source of endogenous arginine before weaning and expresses all of the enzymes necessary for producing arginine from glutamine/glutamate and proline at birth. Therefore, these enzymes may be expressed in the small intestine of the developing fetus. Products of this pathway may be secreted into the fetal circulation for use by the developing fetus or by the fetal small intestine. Understanding the morphological and cytological changes and the expression pattern of these enzymes is necessary for elucidating a functional role for the developing fetal small intestine in amino acid metabolism during gestation.;We used the pig to study the morphological and cytological changes that occur in the mucosa of the fetal small intestine during gestation. Between d 30 and d 110 of gestation the fetal porcine small intestine develops from a simple tube into an organ resembling that of the neonatal animal. The epithelium differentiates, at the cellular and ultrastructural levels, into absorptive, goblet, and enteroendocrine cells.;We determined the expression patterns of four amino acid metabolizing enzymes in developing fetal porcine small intestine. OAT, CPSI, OCT, and P5CR were expressed in fetal porcine small intestine from d 30 to d 110 of gestation. Their expression patterns are similar, suggesting that the majority of the mucosal epithelium is capable of synthesizing proline, ornithine, and arginine. This indicates a functional role for the fetal small intestine in amino acid metabolism during gestation.;We investigated effects of all-trans retinoic, acid (RA) on mRNA expression and enzymatic activity of ornithine aminotransferase in the Caco-2 intestinal epithelial cell line. RA stimulates differentiation in these cells and induced an increase in OAT expression and activity in conjunction with a decrease in proliferation and a decrease in intracellular ornithine.;The results presented in this dissertation suggest that the fetal small intestine plays a role in amino acid metabolism during gestation, which may be regulated by numerous factors, including RA. |
