INDUCTION OF APOPTOSIS BY GONADOTROPIN RELEASING HORMONE DURING PREGNANCY

这个实验室的研究结果表明，服用一种 促性腺激素释放激素激动剂(GnRH-Ag；WY-40972)抑制黄体生成 孕鼠孕酮(P)的合成与释放我们有 证明体内或体外给药GnRH-Ag 在治疗后12小时内抑制黄体合成 早孕时卵巢P的分泌处于控制之下 脑下垂体。我们实验室的最新数据支持这一假设 GnRH-Ag可诱导孕期大鼠黄体细胞凋亡。 因此，当前提案的目的是调查GnRH如何- 银杏叶提取物诱导妊娠早期大鼠CL细胞凋亡。 我们实验室发展的动物模型将被用来回答 在这项提案中提出的问题。这项建议的具体目标是： (1)确认我们的初步观察结果，即持续给药 GnRH-Ag诱导早孕大鼠CL细胞凋亡 进一步确定这种作用是否由PGF/2α介导。会吗？ 功能性细胞凋亡程序结构细胞凋亡还是结构细胞凋亡？(2) 确定一氧化氮(NO)是否介导了细胞凋亡的诱导 经GnRH-Ag处理的大鼠CL。(3)评估促性腺激素释放激素是否- AG对L有直接作用，是促性腺激素释放激素受体介导的作用； 以及(4)确定GnRH-Ag治疗后P分泌是否下降 处理时间与没有时间的活细胞成正比 经历了细胞凋亡。这项调查的长期目标是 了解导致CL消亡的机制 管理GnRH-AG。拟议的研究结果可能会导致 一种新的避孕方法在人类中的应用 妊娠前2周CL的溶解。

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.