FEMALE REPRODUCTIVE AGING: THE ROLE OF ESTROGEN

女性生殖衰老：雌激素的作用

• 批准号: 6533830
• 负责人: PHYLLIS M. WISE
• 金额: $ 77.11万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533830
• 关键词: aging; estrogens; female reproductive system; hormone regulation /control mechanism

The cessation of reproductive function is one of the most dramatic and fairly rapid endocrine changes in the life of a female and carries profound and broad repercussions. At one time, it was thought that decreasing estradiol concentration, resulting from exhaustion of ovarian follicles, caused the menopause. Now, it is clear that many factors interact to bring about declining reproductive function and the cessation of reproductive cycles. Furthermore, we are beginning to appreciate the most- reproductive state affects multiple functions that extend beyond the traditional reproductive axis. An increasing number and an increasing proportion of women will liver a larger fraction of their lives in the postmenopausal state. Therefore, it is critical that we deepened our understanding of the factors that regulate the transition to acyclicity and, conversely, the impact of transition to acyclicity on the function of multiple systems. The program is organized into five research projects that are supported by one Core. The projects are integrated and coordinated to test the following hypotheses (1) changing estrogen responsiveness governs the health and function of ovarian follicles during aging, (2) age-related and estradiol-dependent alterations in the pattern of expression in the ovarian metalloproteinases and their inhibitors result in abnormalities in follicular development and ovulation, (3) aging and/or the cumulative exposure to estradiol regulate changes in somatotroph and lactotroph function, (4) alterations in glutamatergic and adrenergic regulation of GnRH neurons cause changes in their ability to induce LH surges; and (5) estradiol plays a critical protective role in the brain; therefore, declining estradiol concentrations lead to an increased vulnerability to brain injury and neurodegeneration. An Administrative/Animal ore supports all of the projects, providing organizational planning, integrating results from each project into a more comprehensive overview, and maintaining all animal records and coordinating their optical endocrine treatments and use. We submit this program project proposal because we share interests in interdependent aspects of reproductive aging. A common threat that weaves through all of the projects is our interests in the role of estradiol in aging. Finally, this mechanism of support will permit us to use aging animals in the most optimal manner, allowing us to compare data and economize on the costs of aging animals.

停止生殖功能是女性生活中最戏剧性，最快的内分泌变化之一，并带来了深远而广泛的影响。有一次，人们认为雌二醇浓度降低，导致卵巢卵泡的耗尽引起更年期。现在，很明显，许多因素相互作用以引起生殖功能下降和生殖周期的停止。此外，我们开始欣赏最生殖的状态会影响超出传统生殖轴的多种功能。越来越多的妇女将在绝经后的妇女肝脏中肝脏的一部分。因此，至关重要的是，我们加深对调节过渡到环境的因素的理解，相反，过渡到无环的影响对多个系统功能的影响。该计划分为五个由一个核心支持的研究项目。将项目进行整合和协调以检验以下假设（1）改变雌激素反应能力控制衰老过程中卵巢卵泡的健康和功能，（（2）与年龄相关的和雌二醇依赖性依赖性和雌二醇依赖性变化，在卵巢金属蛋白酶及其抑制剂中的表达模式及其在卵泡形成和卵泡形成中的异常（3）或卵泡性的抑制作用（3）雌二醇调节乳腺营养功能的变化，（4）GNRH神经元的谷氨酸能和肾上腺素能调节的改变会导致其诱导LH潮流的能力变化； （5）雌二醇在大脑中起关键的保护作用；因此，雌二醇浓度下降导致对脑损伤和神经退行性的脆弱性增加。行政/动物矿石支持所有项目，提供组织计划，将每个项目的结果整合到更全面的概述中，并维护所有动物记录并协调其光学内分泌治疗和使用。我们提交该计划项目建议，因为我们在生殖衰老的相互依存方面具有利益。在所有项目中编织的一个普遍威胁是我们对雌二醇在衰老中的作用的利益。最后，这种支持机制将使我们能够以最佳的方式使用衰老的动物，从而使我们可以比较数据并节省衰老动物的成本。