REGULATION OF GENE EXPRESSION IN THE AGING OVARY

衰老卵巢中基因表达的调节

• 批准号: 3453628
• 负责人: PHILIP S LAPOLT
• 金额: $ 10.22万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-25 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453628
• 关键词: aging; animal puberty; chorionic gonadotropin; endopeptidases; estrus; female; fertility; follicle stimulating hormone; gene expression; genetic regulation; graafian follicles; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; inhibin; juvenile animal; laboratory rat; luteinizing hormone; messenger RNA; neuroendocrine system; northern blottings; ovariectomy; ovulation; radioimmunoassay; western blottings

The decline in fertility with advanced age has emerged as an important issue in reproductive medicine. In this regard, the female rat has provided a relevant and practical modes to study reproductive aging. In the rat and human, reproductive senescence is preceded by neuroendocrine and ovarian impairments which are reflected by altered patterns of gonadotrophin secretion, ovarian follicular development, and ovulation. However, the relationships between circulating gonadotropin levels and changes in ovarian functions preceding reproductive senescence are not well understood. Therefore, the proposed studies are designed to explore the relationships between age-related changes in neuroendocrine function and potential alterations in ovarian gene expression and response to gonadotrophins in regularly cyclic middle-aged female rats. Specifically, the aims of this proposal are: l) To examine whether there is a prolongation of the secondary FSH surge in rats with decreased follicular pools (intact middle-aged rats and hemiox young and middle-aged females, as compared with intact young females), and to determine the relationship between secondary FSH surge profiles and ovarian inhibin gene expression; 2) To assess the relationships between the magnitudes of endogenous LH and FSH surges, ovulation rate, and induced expression of ovarian proteolytic enzymes mediating follicle rupture in regularly cyclic, middle-aged and young female rats; 3) To compare ovarian sensitivity and maximal ovulatory and proteolytic responses to exogenous hCG stimulation in middle-aged and young cyclic rats. Similarly, to assess relative induction of ovarian proteinase expression and ovulation by exogenous recombinant FSH to determine whether age-related changes in ovulatory response are specific to LH stimulation. The findings from these studies will provide new insights regarding the roles of the neuroendocrine system and ovary in the onset of reproductive senescence. Furthermore, age-related changes in neuroendocrine and ovarian function in the aging female rat provide a useful model to study dynamic interactions between hypothalamus, pituitary and ovary. Ultimately, it is hoped that these findings may result in the development of new clinical strategies relevant to age-related declines in human reproductive function.

随着年龄的增长，生育率的下降已经成为一个重要的 生殖医学中的问题。在这方面，雌性老鼠有 为生殖衰老的研究提供了相关的、实用的模式。在……里面 大鼠和人的生殖衰老是由神经内分泌引起的 和卵巢损伤，反映在改变的模式 促性腺激素分泌、卵泡发育和排卵。 然而，循环促性腺激素水平与 在生殖衰老之前卵巢功能的变化不是 很好理解。因此，拟议的研究旨在探索 增龄与神经内分泌功能变化的关系 以及卵巢基因表达和反应的潜在变化 周期性中年雌性大鼠促性腺激素的变化。 具体地说，这项建议的目的是： L)检查是否存在二次促卵泡激素高峰的延长 在卵泡池减少的大鼠(完整的中年大鼠和 与完整的年轻女性相比，年轻和中年女性 女性)，并确定继发性FSH峰之间的关系 卵巢抑制素基因的表达； 2)评估内源性促黄体生成素水平之间的关系 和FSH激增，排卵率和卵巢诱导表达 蛋白水解酶在有规律的循环中介导卵泡破裂， 中青年雌性大鼠； 3)比较卵巢敏感性、最大排卵量和最大蛋白水解率 中青年周期对外源性hCG刺激的反应 老鼠。同样，评估卵巢蛋白水解酶的相对诱导性 外源重组FSH的表达和排卵测定 排卵反应的年龄相关变化是否为黄体生成素所特有 刺激。 这些研究的发现将提供关于 神经内分泌系统和卵巢在生殖启动中的作用 衰老。此外，与年龄相关的神经内分泌和 老年雌性大鼠卵巢功能研究提供了有用的模型 下丘脑、垂体和卵巢之间的动态相互作用。 最终，人们希望这些发现可能会导致 与人类年龄相关性下降相关的新临床策略 生殖功能。