GNRH EFFECTS ON LUTEAL FUNCTION DURING GESTATION IN RATS

这个实验室以前的研究表明， 促性腺激素释放激素(GnRH)或其激动型类似物(GnRH-Ag； WY-40972)在24小时内抑制血浆孕酮(P)水平， 随后导致流产；这种治疗也抑制了核 黄体(CL)中的雌二醇受体，并降低 在这24小时内，催乳素(PRL)出现夜间高峰。初级阶段 这项研究提案的目标是确定准确的位置，或 可能是促性腺激素释放激素抗生育作用的基因座 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小时内抑制黄体P分泌。首先，将测定 GnRH-Ag的抗妊娠作用是否通过抑制 孕期促乳素(S)。在今年上半年 怀孕时，(I)将在CL水平上测量PRL受体；(Ii)它 将确定PRL替代疗法是否将血浆P水平恢复到正常水平 GnRH-Ag处理的大鼠；如果P或E替代恢复大鼠 催乳素夜间上升至正常；(3)蜕膜促黄体素水平 将测量蜕膜中的(一种催乳素样激素)；(Iv)垂体催乳素 水平及其GnRH受体含量将被测量，以及(V)影响 GnRH-Ag在类固醇环境中对催乳素合成和分泌的影响 将使用单层细胞对分散的垂体细胞进行评估 文化和灌输系统。在怀孕的后半段， 颈静脉和子宫静脉血浆中胎盘催乳素水平 以及在CL的滋养层组织和PRL受体中，将 量过了。将确定是否在上半年更换了PRL 或在妊娠后半期更换大鼠胎盘催乳素 适量会恢复核内雌二醇水平 CL中的PRL受体和PRL受体恢复正常。接下来，牵涉到 促性腺激素释放激素对黄体P合成的影响将通过测量 人绒毛膜促性腺激素对黄体合成睾酮、雌二醇和P的影响 体外治疗。最后，将确定黄体是否 促性腺激素释放激素对黄体的直接抑制作用 黄体P的类固醇生成和/或胆固醇可利用性 综合。结果将表明受体结合参与其中。 雌激素在胆固醇转运中的作用及促性腺激素释放激素对其的影响。这些 研究将加深我们对促性腺激素释放激素作用机制的理解 在怀孕期间。

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.