LUTEOTROPHIC ACTIONS OF INSULIN-LIKE GROWTH FACTOR-I

胰岛素样生长因子 I 的促黄体营养作用

• 批准号: 3329998
• 负责人: PAUL LANDIS KEYES
• 金额: $ 10.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3329998
• 关键词: estradiol; estrogens; glucose transport; hormone regulation /control mechanism; laboratory rabbit

The corpus luteum is the ovarian structure that produces progesterone, a hormone that is essential for the maintenance of pregnancy. The corpus luteum is stimulated to produce progesterone by hormones or factors, called luteotrophins. In the rabbit, the principal luteotrophin is estrogen, produced by the ovarian follicles. From preliminary studies and other information, we propose a new concept for the luteotrophic process in the rabbit: estrogen stimulates the production of insulin-like growth factor-I and/or insulin-like growth factor-II (IGF-I/IGF-II) by luteal cells, and IGF-I/IGF-II then acts in an autocrine or paracrine manner to stimulate metabolism and steroidogenesis by luteal cells. To test this hypothesis, we will use several approaches, each with particular advantage to manipulate the luteotrophic milieu: luteal tissue obtained from estrogen- treated animals, and from normal pseudopregnant and pregnant rabbits; luteal tissue in organ culture; and luteal cells in monolayer culture, in which steroidogenesis is strikingly maintained by IGF-I. Using these approaches, experiments will be conducted to determine: a) whether IGF-I and/or IGF-II, their receptors, and mRNA for IGF-I are expressed in specific cell types of the corpus luteum as revealed by light - and electron - microscopic immunocytochemistry and in situ hybridization; and whether this expression changes with estrogen stimulation and in different stages of the luteal phase and pregnancy as determined by computer-based image analysis and quantitative morphometry; b) whether IGF-I binds to type I or type II receptors, and whether these receptors can be regulated by estrogen, and change during different stages of pseudopregnancy and pregnancy; c) whether IGF-I/IGF-II has a trophic action by producing insulin-like metabolic effects in luteal cells; d) whether steroidogenesis by rabbit luteal tissue is attributable to an autocrine/paracrine action of IGF-I/IGF-II.

黄体是产生孕酮的卵巢结构， 维持怀孕所必需的激素。 语料库 黄体被激素或因子刺激产生孕酮，称为 促黄体生成素 在兔子体内，主要的促黄体激素是雌激素， 由卵巢卵泡产生。 从初步研究和其他 信息，我们提出了一个新的概念，在黄体营养过程中， 兔子：雌激素刺激胰岛素样生长因子-I的产生 和/或胰岛素样生长因子-II（IGF-I/IGF-II），和 然后IGF-I/IGF-II以自分泌或旁分泌的方式起作用， 代谢和黄体细胞的类固醇生成。 为了验证这个假设， 我们将使用几种方法，每种方法都具有特定的优势， 操纵促黄体环境：从雌激素中获得的黄体组织， 给药动物和正常假孕和妊娠兔; 器官培养中的黄体组织;单层培养中的黄体细胞， 其类固醇生成显著地由IGF-I维持。 使用这些 方法，将进行实验以确定：a）IGF-I是否 和/或IGF-II、它们的受体和IGF-I的mRNA表达于 通过光和电镜观察， 电子显微镜免疫细胞化学和原位杂交;和 这种表达是否随着雌激素刺激而改变，以及在不同的 黄体期和怀孕的阶段，由计算机确定的 图像分析和定量形态测定; B）IGF-I是否结合型 I型或II型受体，以及这些受体是否可以通过 雌激素，以及假孕不同阶段的变化， c）IGF-I/IGF-II是否通过产生 黄体细胞中的胰岛素样代谢作用; d）类固醇生成是否 的自分泌/旁分泌作用， IGF-I/IGF-II。