INDUCTION OF APOPTOSIS BY GONADOTROPIN RELEASING HORMONE DURING PREGNANCY

妊娠期间促性腺激素释放激素诱导细胞凋亡

• 批准号: 6204190
• 负责人: Rajagopala Sridaran
• 金额: $ 9.59万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6204190
• 关键词: apoptosis; corpus luteum; early embryonic stage; fertility; gonadotropin releasing factor; hormone regulation /control mechanism; laboratory rat; nitric oxide; northern blottings; pregnancy; prostaglandin F; radioimmunoassay; steroid biosynthesis; western blottings

The findings from this laboratory suggest that administration of a gonadotropin-releasing hormone agonist (GnRH-Ag; WY-40972) inhibits luteal progesterone (P) synthesis and release in pregnant rats. We have demonstrated that in vivo or in vitro administration of a GnRH-Ag suppresses luteal synthesis within 12 hours after the treatment during early pregnancy when the ovarian P secretion is under the control of pituitary. The recent data from our laboratory support the hypothesis that GnRH-Ag induces apoptosis in the rat corpus luteum (CL) during pregnancy. Therefore, the purpose of the current proposal is to investigate how GnRH- Ag induces apoptotic cell death in the CL during early pregnancy in rats. The animal model developed in our laboratory will be used to answer the questions raised in this proposal. The specific aims of this proposal are: (1) To confirm our preliminary observations that continuous administration of GnRH-Ag induces apoptosis in the rat CL during early pregnancy and to further determine whether the effect is mediated by PGF/2alpha. Does functional apoptosis procedure structural apoptosis or vice versa? (2) To determine if nitric oxide (NO) mediates the induction of apoptosis in the rat CL by the GnRH-Ag treatment. (3) To assess whether the effect of GnRH- Ag is a direct effect on the L which is a GnRH receptor mediated effect; and (4) To determine whether the decline in P secretion after the GnRH-Ag treatment with time is proportional to viable cells that have not undergone apoptosis. The long-term goal of this investigation is to understand the mechanisms involved in inducing the demise of the CL by administering a GnRH-AG. The results of the proposed study could lead to an application of a new approach to contraception in the human by inducing the lysis of the CL during the first 2 weeks of pregnancy.

该实验室的研究结果表明， 促性腺激素释放激素激动剂（GnRH-Ag; WY-40972）抑制黄体生成素（LH）分泌 孕鼠孕酮（P）的合成和释放。我们有 证明体内或体外给予GnRH-Ag 在治疗后12小时内抑制黄体合成， 妊娠早期，当卵巢P分泌受到控制时， 脑垂体我们实验室最近的数据支持这样一种假设， GnRH-Ag诱导妊娠大鼠黄体细胞凋亡。 因此，本提案的目的是研究GnRH- Ag诱导大鼠妊娠早期CL细胞凋亡。 我们实验室开发的动物模型将用于回答 这一提案中提出的问题。这项建议的具体目标是： (1)为了证实我们的初步观察， GnRH-Ag诱导大鼠妊娠早期CL细胞凋亡， 进一步确定该作用是否由PGF/2 α介导。并 功能性凋亡过程是结构性凋亡还是相反？(2)到 确定一氧化氮（NO）是否介导细胞凋亡的诱导， GnRH-Ag治疗大鼠CL。(3)为了评估GnRH的作用- Ag对L的直接作用是GnRH受体介导的作用; （4）探讨GnRH-Ag治疗后P分泌的下降是否与GnRH-Ag治疗后P分泌的下降有关。 处理与时间成正比的活细胞， 经历了凋亡。这项调查的长期目标是 了解诱导CL死亡的机制， 给予GnRH-AG。拟议研究的结果可能导致 一种新的避孕方法的应用， 在妊娠的前2周内CL的溶解。