STUDIES IN GASTROINTESTINAL ENDOCRINOLOGY

该计划的长期目标是提供新的，有用的 关于胃肠激素（GIH）和 相关化合物影响身体功能。 我们计划研究合成， 储存、释放、运输以及这些药剂对 靶细胞，靶细胞反应，激素相互关系 以及它们的基因表达。 在项目1中，我们 研究与年龄相关的胃肠道激素变化的机制 代谢以及肠道和胰腺对营养刺激的反应。 我们 将确定年龄相关的GI变化的机制， 功能可能与疾病的发展有关。 在项目2中，我们 检查嗜铬粒蛋白的相关性及其在胃肠道中的生理作用 胰管和胰腺。 我们将研究胰蛋白酶抑制剂对 胰腺释放胰岛素。 在项目3中，我们将检查 GIH激素对癌症生长的影响。 我们将研究 的营养作用。 我们将确定生长因子的作用， 控制胃肠道和胰腺癌的生长。 在项目4中，我们 探讨甲状旁腺相关蛋白mRNA的表达， 降钙素基因相关肽。 我们将 确定肽在肠道中的位置， 并检查细胞对mRNA表达的调节。 在项目5中，我们将定义细胞和细胞内机制， 调节类固醇对肠道和胰腺功能的影响， 结肠癌和胰腺癌细胞的生长。 我们将描述 来自各种肠道和胰腺组织的雌二醇结合蛋白。 我们 建立了一个新的分子病理学核心，研究 营养性肠肽对细胞周期相关基因表达的影响 自分泌生长因子的表达。 组织学定位 神经肽基因表达和调节机制，影响 将检查表达水平。 自从上次竞争性审查以来， 我们的出版物表明，我们的合作已经 多产;许多出版物涉及一个以上的项目。 与 在这项资助的支持下，我们继续进一步扩大深度， 我们的研究广度，以满足这一计划的长期目标。

The long-term objective of this program is to provide new, useful information on the mechanisms by which gastrointestinal hormones (GIH) and related compounds influence body function. We plan to study the synthesis, storage, release, transport, and mechanisms of action of these agents on target cells, target-cell responses, the hormone-hormone interrelationships of these peptides, and their gene expression. In Project 1, we will examine the mechanisms underlying age-related changes in GI hormone metabolism and in responses of the gut and pancreas to trophic stimuli. We will determine the mechanisms by in which age-related changes in GI function may relate to development of disease. In Project 2, we will examine the relevance of chromogranin and its physiologic role in the GI tract and pancreas. We will investigate the action of pancreastatin on the release of insulin from the pancreas. In Project 3, we will examine the effects of GIH hormones on growth of cancers. We will study the mechanisms of trophic actions of GIH. We will determine the role of growth factors in control of growth of GI and pancreatic cancers. In Project 4, we will explore expression of mRNA for parathyroid hormone-related protein and calcitonin gene-related peptide by gut tissues and cells. We will determine the location of the peptides in the gut, identify cellular sites of synthesis and examine the regulation of mRNA expression by the cells. In Project 5, we will define cellular and intracellular mechanisms that mediate effects of steroids on functions of gut and pancreas and on the growth of colonic and pancreatic cancer cells. We will characterize estradiol-binding proteins from various gut and pancreatic tissues. We have established a new Molecular Pathobiology Core to study the effects of trophic gut peptides on expression of cell cycle-related genes and on the expression of autocrine growth factors. Histological localization of neuropeptide gene expression and regulatory mechanisms that affect the level of expression will be examined. Since the last competitive review, we have demonstrated by our publications that our collaboration has been productive; many publications relate to more than one project. With the support of this grant, we have continued to further expand the depth and breadth of our research to meet the long-term objective of this program.