PEPTIDE YY EXPRESSION IS AN EARLY EVENT IN COLONIC ENDOCRINE CELL-DIFFERENTIATION - EVIDENCE FROM NORMAL AND TRANSGENIC MICE

The hormone peptide YY is produced by endocrine cells in the pancreas, ileum and colon, We have previously shown that peptide YY is coexpres sed in all four islet cell types in the murine pancreas when they firs t appear, suggesting a common peptide YY-producing progenitor, Tn the colon, peptide YY has been frequently identified in glucagon-expressin g L-type endocrine cells, Characterization of colonic endocrine tumors in transgenic mice expressing simian virus 40 large T antigen under t he control of the peptide YY gene 5' flanking region revealed tumor ce lls producing not only peptide YY and glucagon, but also neurotensin, cholecystokinin, substance P, serotonin, secretin, and gastrin, This s uggested that multiple enteroendocrine lineages were related to peptid e YY-producing cells, Subsequent examination of the ontogeny of coloni c endocrine differentiation in nontransgenic mice revealed that peptid e YY was the first hormone to appear during development, at embryonic day 15.5, Between embryonic days 16.5 and 18.5, cells expressing gluca gon, cholecystokinin, substance P, serotonin, secretin, neurotensin, g astrin and somatostatin first appeared and peptide YY was coexpressed in each cell type at this time, Peptide YY coexpression continued in a significant fraction of most enteroendocrine cell types throughout fe tal and postnatal development and into adulthood, with the exception o f serotonin-producing cells, This latter population of cells expanded dramatically after birth with rare coexpression of peptide YY. These s tudies indicate that expression of peptide YY is an early event in col onic endocrine differentiation and support the existence of a common p rogenitor for all endocrine cells in the colon.