REGULATORY MECHANISMS OF OVARIAN PROGESTERONE RECEPTORS

卵巢孕酮受体的调节机制

• 批准号: 2673329
• 负责人: Ok-Kyong Park-Sarge
• 金额: $ 6.48万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673329
• 关键词: DNA footprinting; aging; biological signal transduction; cyclic AMP; estrogens; female; follicle stimulating hormone; gel mobility shift assay; genetic promoter element; genetic regulatory element; genetic transcription; granulosa cell; hormone regulation /control mechanism; in situ hybridization; laboratory rat; luteinizing hormone; northern blottings; nucleic acid sequence; progesterone receptors; protein isoforms; protein kinase A; protein kinase C; receptor expression; site directed mutagenesis; tissue /cell culture

Dr. Ok-Kyong Park-Sarge was appointed an Assistant Professor in the Department of Physiology in July 1993. She has demonstrated outstanding competence as a biomedical researcher during the last 18 months. She was awarded an NIH FIRST AWARD (R29) and has applied for pilot funds from both the Markey Cancer Center and the Center on Aging at the University of Kentucky. She is a member of the NIH-funded Reproductive Sciences Training Program and actively interacts with members of the markey Cancer Center and the Center on Aging. At the present time, teaching and service activities comprise about 50% of her effort. With support from an RCDA, Dr. Park- Sarge would be relieved of formal teaching and service activities and would be able to concentrate on the conduct or supervision of research including supervision of graduate students or postdoctoral fellows. A significant reduction in her teaching and service activities would also allow Dr. Park- Sarge to obtain research training in several techniques important for future studies. Dr Park-Sarge's research has focused on the regulatory mechanisms of the progesterone receptor gene in tahe ovary. The observation she made during her postdoctoral training period, that the ovary transiently expresses the progesterone receptor gene in granulosa cells of preovulatory follicles during the period critical for ovulatory processes, clearly suggests that the ovary is a target of autocrine or paracrine action of progesterone. She has further determined that the primary mechanism regulating the progesterone receptor gene in this tissue is through activation of membrane receptors for gonadotropins. Thus, these findings reveal a striking difference between regulation of the progesterone receptor gene int he ovary compared to any other progesterone receptor-containing tissue. Her long-term goal is to better understand athe role of ovarian progesterone receptors in the regulation of fertility in normal and dysfunctional reproductive processes. Her immediate goal is to determine the molecular mechanisms for gonadotropin-stimulated progesterone receptor transcription in the ovary. During the award period, she will examine the cellular and molecular mechanisms of progesterone receptor gene transcription. She will determine the role of protein kinase A and C in gonadotropin-stimulated progesterone receptor expression in granulosa cells and define cis-regulatory sequences that mediate gonadotropin-induced PR expression. In addition, she will determine the basis of the lack of estrogen-stimulated activation of this gene. Moreover, she will apply athe information on PR expression in young female rats to aging female rats to examine whether age-related alterations of PR expression may explain some of the observed changes that occur during reproductive aging. Her interaction with members of the reproductive biology group, the Markey Cancer Center, and the Center on Aging at the University of Kentucky will facilitate her growth as a leader within the scientific community. A strong commitment to Dr. Park-Sarge from the University of Kentucky together with the RCDA will make a critical difference in Dr. Park-Sarge's future status as leader within the scientific community.

博士. Ok-Kyong Park-Sarge被任命为助理教授在 1993年7月，生理学系。 她表现出了杰出的 在过去的18个月里，作为一名生物医学研究人员。 她 获得了NIH第一奖（R29），并已申请了两个试点基金 马基癌症中心和老龄化中心在大学 肯塔基州。 她是NIH资助的生殖科学培训的成员 计划并积极与马基癌症中心的成员互动， 老龄化中心。 目前，教学和服务活动 占了她50%的努力 在RCDA的支持下，帕克博士- 中士将被解除正式的教学和服务活动， 能够集中精力进行或监督研究，包括 对研究生或博士后研究员的监督。 显著 减少她的教学和服务活动也将允许朴博士- 中士获得研究培训，在几个重要的技术， 未来的研究。 Park-Sarge博士的研究主要集中在 卵巢孕酮受体基因。 她的观察 她的博士后培训期间，卵巢瞬时表达 排卵前卵泡颗粒细胞孕酮受体基因 在排卵过程的关键时期，清楚地表明 卵巢是孕酮自分泌或旁分泌作用的靶点。 她还进一步确定， 孕激素受体基因在这个组织是通过激活膜 促性腺激素受体 因此，这些发现揭示了一个惊人的 孕激素受体基因的调控与人类生殖系统的差异 卵巢相比，任何其他孕激素受体含有组织。 她 长期目标是更好地了解卵巢孕酮的作用 受体在正常和功能失调的生育调节中的作用 生殖过程 她的近期目标是确定 卵巢中促性腺激素刺激的孕酮受体转录。 在颁奖期间，她将检查细胞和分子 孕酮受体基因转录的机制。 她会决定 蛋白激酶A和蛋白激酶C在促性腺激素促孕激素分泌中作用 受体在颗粒细胞中的表达并确定顺式调节序列 介导促性腺激素诱导的PR表达。 此外，她将 确定缺乏雌激素刺激激活这一基础 基因 此外，她将在年轻人的公关表达中应用大量信息， 雌性大鼠到衰老雌性大鼠，以检查是否与年龄有关的变化 PR表达的变化可以解释一些观察到的变化， 生殖老化 她与生殖组织成员的互动 生物学小组，马基癌症中心和老龄化中心在 肯塔基州的大学将促进她的成长为一个领导者在 科学界。 对来自肯塔基州大学的Park-Sarge博士的坚定承诺 与RCDA一起将在Park-Sarge博士的 未来在科学界的领导地位。