Upchurch B H, Fung B P, Rindi G, Ronco A, Leiter A B
Division of Gastroenterology, Tupper Research Institute, New England Medical Center-Tufts University School of Medicine, Boston, MA 02111, USA.
Development. 1996 Apr;122(4):1157-63. doi: 10.1242/dev.122.4.1157.
The hormone peptide YY is produced by endocrine cells in the pancreas, ileum and colon. We have previously shown that peptide YY is coexpressed in all four islet cell types in the murine pancreas when they first appear, suggesting a common peptide YY-producing progenitor. In the colon, peptide YY has been frequently identified in glucagon-expressing L-type endocrine cells. Characterization of colonic endocrine tumors in transgenic mice expressing simian virus 40 large T antigen under the control of the peptide YY gene 5' flanking region revealed tumor cells producing not only peptide YY and glucagon, but also neurotensin, cholecystokinin, substance P, serotonin, secretin, and gastrin. This suggested that multiple enteroendocrine lineages were related to peptide YY-producing cells. Subsequent examination of the ontogeny of colonic endocrine differentiation in nontransgenic mice revealed that peptide YY was the first hormone to appear during development, at embryonic day 15.5. Between embryonic days 16.5 and 18.5, cells expressing glucagon, cholecystokinin, substance P, serotonin, secretin, neurotensin, gastrin 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 fetal and postnatal development and into adulthood, with the exception of serotonin-producing cells. This latter population of cells expanded dramatically after birth with rare coexpression of peptide YY. These studies indicate that expression of peptide YY is an early event in colonic endocrine differentiation and support the existence of a common progenitor for all endocrine cells in the colon.
激素肽YY由胰腺、回肠和结肠中的内分泌细胞产生。我们之前已经表明，肽YY在小鼠胰腺中首次出现时，在所有四种胰岛细胞类型中共同表达，这表明存在一个共同的产生肽YY的祖细胞。在结肠中，肽YY经常在表达胰高血糖素的L型内分泌细胞中被发现。在肽YY基因5'侧翼区域控制下表达猿猴病毒40大T抗原的转基因小鼠中，对结肠内分泌肿瘤的特征分析显示，肿瘤细胞不仅产生肽YY和胰高血糖素，还产生神经降压素、胆囊收缩素、P物质、5-羟色胺、促胰液素和胃泌素。这表明多个肠内分泌谱系与产生肽YY的细胞有关。随后对非转基因小鼠结肠内分泌分化个体发育的检查发现，肽YY是发育过程中最早出现的激素，在胚胎第15.5天出现。在胚胎第16.5天至18.5天之间，表达胰高血糖素、胆囊收缩素、P物质、5-羟色胺、促胰液素、神经降压素、胃泌素和生长抑素的细胞首次出现，此时肽YY在每种细胞类型中共同表达。在整个胎儿期、出生后发育直至成年期，除了产生5-羟色胺的细胞外，肽YY在大多数肠内分泌细胞类型的很大一部分中持续共同表达。后一组细胞在出生后急剧扩增，很少与肽YY共同表达。这些研究表明，肽YY的表达是结肠内分泌分化中的早期事件，并支持结肠中所有内分泌细胞存在共同祖细胞的观点。
