FEMALE REPRODUCTIVE AGING-- THE ROLE OF ESTROGEN

女性生殖衰老——雌激素的作用

• 批准号: 6131828
• 负责人: PHYLLIS M. WISE
• 金额: $ 71.93万
• 依托单位: UNIVERSITY OF KENTUCKY
• 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/6131828
• 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.

生殖功能的停止是女性一生中最显着且相当迅速的内分泌变化之一，并带来深远而广泛的影响。曾几何时，人们认为卵巢卵泡衰竭导致雌二醇浓度下降导致更年期。现在，很明显，许多因素相互作用，导致生殖功能下降和生殖周期停止。此外，我们开始认识到最具生殖能力的状态会影响超出传统生殖轴的多种功能。越来越多、越来越多的女性将在绝经后状态下度过一生的大部分时间。因此，加深对调节非周期性转变的因素以及非周期性转变对多个系统功能的影响的理解至关重要。该计划分为五个研究项目，由一个核心支持。这些项目经过整合和协调，以测试以下假设：(1) 雌激素反应性的变化控制着衰老过程中卵巢卵泡的健康和功能，(2) 卵巢金属蛋白酶及其表达模式的与年龄相关和雌二醇依赖性的改变抑制剂导致卵泡发育和排卵异常，（3）衰老和/或累积暴露于雌二醇调节生长激素和催乳素功能的变化，（4） GnRH 神经元的谷氨酸能和肾上腺素能调节导致其诱导 LH 激增的能力发生变化； (5)雌二醇对大脑具有重要的保护作用；因此，雌二醇浓度下降会导致脑损伤和神经退行性疾病的脆弱性增加。行政/动物矿石支持所有项目，提供组织规划，将每个项目的结果整合为更全面的概述，并维护所有动物记录并协调其光学内分泌治疗和使用。我们提交此计划项目提案是因为我们在生殖衰老的相互依存方面有着共同的利益。贯穿所有项目的一个共同威胁是我们对雌二醇在衰老中的作用的兴趣。最后，这种支持机制将使我们能够以最优化的方式使用老龄动物，使我们能够比较数据并节省老龄动物的成本。