HORMONE MEDIATED REGULATION OF OVARIAN FUNCTION

激素介导的卵巢功能调节

• 批准号: 7381195
• 负责人: Thomas E Curry
• 金额: $ 25.05万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381195
• 关键词: HORMONE; MEDIATED; REGULATION; OVARIAN; FUNCTION

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project explores estrogen action on the ovary and the mammary gland. Studies conducted during the past funding period have explored the changes in 1) the ovarian matrix metalloproteinases, 2) ovarian gene expression, and 3) a class of nuclear hormone receptors, the peroxisome proliferator-activated receptors (PPARs), in mammary gland function. All four of the investigators associated with this project have made significant progress towards their individual experiments as well as towards establishing preliminary data for the competitive renewal of this Project. Dr. Misung Jo is continuing to examine the functional significance of a novel gene, Runx1, in late follicle development. The localization pattern of Runx1 expression and the mechanism(s) of Runx1 expression continue to shed light on the functional role this protein plays in follicular development and ovulation. Preliminary experiments with silencing RNA have suggested that Runx1 may mediate the LH induced increase in progesterone production. Experiments by Dr. Michael Kilgore have continued to investigate the signal crosstalk between the estrogen receptor beta (ERb) and the peroxisome proliferator-activated receptor gamma (PPARg). Preliminary data indicates that crosstalk between these receptors results in gene-specific changes with a number of genes being upregulated while other genes are downregulated as seen by DNA microarray. Ongoing studies are examining the significance of these changes in gene expression on cellular proliferation and migration. Finally, a series of breeding experiments by Dr. Jay Ko have been in progress to generate tissue-specific knockouts of the estrogen receptor (ER) isoforms. These ongoing studies are creating mice which lack ERa or ERb in the oocyte, the granulosa cell, or the theca cells. To date, oocyte-specific estrogen receptor knockout have been generated which lack ERa. These mice exhibit a reduced ovulatory capacity although they are fertile. The impact of estrogen action on the theca and granulosa cell layers of the follicle will be explored as these mice become available. In Dr. Curry's laboratory, the role and timing of expression of the matrix metalloproteinase-19 and its inhibitors in ovarian development and ovulation continues to be unraveled. These studies demonstrate the importance of tissue remodeling in regulating ovarian function and fertility. Therefore, all the projects have made significant progress in developing the necessary tools to address the goals of each project and are in an excellent position to provide convincing data for the competitive renewal of the COBRE project as well as compete for extramural support.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。该项目探讨雌激素对卵巢和乳腺的作用。过去资助期间进行的研究探索了乳腺功能中 1) 卵巢基质金属蛋白酶、2) 卵巢基因表达和 3) 一类核激素受体——过氧化物酶体增殖物激活受体 (PPAR) 的变化。与该项目相关的所有四名研究人员在各自的实验以及为该项目的竞争性更新建立初步数据方面都取得了重大进展。 Misung Jo 博士正在继续研究一种新基因 Runx1 在卵泡发育后期的功能意义。 Runx1 表达的定位模式和 Runx1 表达的机制继续阐明该蛋白在卵泡发育和排卵中发挥的功能作用。沉默 RNA 的初步实验表明 Runx1 可能介导 LH 诱导的黄体酮生成增加。 Michael Kilgore 博士的实验继续研究雌激素受体 β (ERb) 和过氧化物酶体增殖物激活受体 γ (PPARg) 之间的信号串扰。初步数据表明，这些受体之间的串扰导致基因特异性变化，如 DNA 微阵列所见，许多基因上调，而其他基因下调。正在进行的研究正在研究基因表达的这些变化对细胞增殖和迁移的重要性。最后，Jay Ko 博士正在进行一系列育种实验，以产生雌激素受体 (ER) 同工型的组织特异性敲除。这些正在进行的研究正在培育卵母细胞、颗粒细胞或卵泡膜细胞中缺乏 ERa 或 ERb 的小鼠。迄今为止，已经产生了缺乏 ERa 的卵母细胞特异性雌激素受体敲除技术。这些小鼠虽然具有生育能力，但排卵能力下降。当这些小鼠变得可用时，将探讨雌激素作用对卵泡膜和颗粒细胞层的影响。在 Curry 博士的实验室中，基质金属蛋白酶 19 及其抑制剂在卵巢发育和排卵中的作用和表达时间仍有待阐明。这些研究证明了组织重塑在调节卵巢功能和生育能力方面的重要性。因此，所有项目在开发实现每个项目目标所需的工具方面都取得了重大进展，并且处于有利地位，可以为 COBRE 项目的竞争性更新提供令人信服的数据，并竞争外部支持。