GNRH EFFECTS ON LUTEAL FUNCTION DURING GESTATION IN RATS

该实验室先前的研究表明， 促性腺激素释放激素（GnRH）或其激动类似物（GnRH-Ag; WY-40972）在24小时内抑制血浆孕酮（P）水平， 随后导致流产;治疗还抑制核 雌二醇受体在黄体（CL），并降低幅度 催乳素（PRL）在这24小时内夜间激增。 主 这项研究计划的目标是确定精确的基因位点，或 可能是GnRH抗生育作用的位点， 其抑制黄体P合成和分泌的机制 在怀孕期间 GnRH-Ag将以有效剂量用于本研究 在24 h内抑制黄体P分泌。 首先，它将确定 如果GnRH-Ag的抗妊娠作用是通过抑制 妊娠期催乳激素。 年上半年 妊娠，（i）将测量CL水平的PRL受体;（ii） 将确定PRL替代是否使血浆P水平恢复正常， GnRH-Ag治疗的大鼠;如果P或E替代恢复了 PRL夜间激增至正常;（iii）蜕膜促黄体激素水平 （一种催乳素样激素）将被测量;（iv）垂体催乳素 水平和它们的GnRH-受体含量将被测量，和（v）作用 激素环境中GnRH-Ag治疗对PRL合成和分泌的影响 将使用单层细胞评估分散的垂体细胞 培养和灌流系统。 在怀孕的后半期， 颈静脉和子宫静脉血浆中的胎盘催乳素水平， 以及在滋养层组织和催乳素受体在CL，将是 测定了 将确定是否在上半场更换PRL 或在妊娠后半期替换的大鼠胎盘催乳素 适当的剂量将恢复细胞核雌二醇的水平 受体和催乳素受体的CL正常。 其次，参与 将通过测量GnRH对LH合成黄体P的影响来检查 黄体对hCG反应性睾酮、雌二醇和P的合成 体外治疗 最后，将确定是否黄体 GnRH对P的抑制是通过其对黄体的直接作用介导的。 类固醇生成和/或胆固醇利用率 合成. 结果将表明受体结合的参与 雌二醇在胆固醇转运中的作用及GnRH对胆固醇转运的影响。 这些 研究将增加我们对GnRH作用机制的理解 孕期

The previous studies in this laboratory have shown that gonadotropin-releasing hormone (GnRH) or its agonistic analog (GnRH-Ag; WY-40972) suppresses plasma progesterone (P) levels within 24 h, which subsequently results in abortion; the treatment also suppresses nuclear estradiol receptors in the luteum (CL) and decreases the magnitude of nocturnal surges of prolactin (PRL) during this 24 h period. The primary goal of this research proposal is to determine the precise locus, or probably the loci, of the antifertility action of GnRH and to understand the mechanism by which it suppresses the luteal P synthesis and secretion during gestation. GnRH-Ag will be used in this study at the effective dose to suppress luteal P secretion within 24 h. First, it will be determined if the antigestational action of GnRH-Ag is mediated by suppressing lactogenic hormone(s) during gestation. During the first half of pregnancy, (i) PRL receptors at the level of CL will be measured; (ii) it will be determined if PRL replacement restores plasma P levels to normal in GnRH-Ag treated rats; if P or E replacement restores the magnitude of nocturnal surge of PRL to normal; (iii) the level of decidual luteotropin (a PRL-like hormone) in the decidua will be measured; (iv) pituitary PRL levels and their GnRH-receptor content will be measured, and (v) the effect of GnRH-Ag treatment in a steroidal milieu on PRL synthesis and secretion by dispersed pituitary cells will be assessed using the monolayer cell culture and perifusion systems. During the second half of pregnancy, the levels of placental lactogen in the jugular and uterine vein plasma, as well as in the trophoblastic tissue and PRL receptors in CL, will be measured. It will be determined if the replaced PRL during the first half or the replaced rat placental lactogen during the second half of pregnancy in the appropriate amounts will restore the levels of nuclear estradiol receptors and of PRL receptors in the CL to normal. Next, the involvement of GnRH over luteal P synthesis through LH will be examined by measuring luteal synthesis of testosterone, estradiol and P in response to hCG treatment in vitro. Finally, it will be determined if the luteal suppression of P by GnRH is mediated by its direct action on luteal steroidogenesis and/or the cholesterol availability for luteal P synthesis. The results will indicate the involvement of receptor bound estradiol in cholesterol transport and GnRH effect on it in the CL. These studies will increase our understanding of the mechanism of action of GnRH during pregnancy.