REGULATION OF THE PRIMATE CORPUS LUTEUM

本研究的长期目标是阐明 导致灵长类动物黄体在排卵期结束时退化， 不生育的月经周期。 本提案的具体目标是 以确定促黄体生成素分泌模式的变化是否 在黄体期的后半部分的激素是负责 黄体退化。 这些研究利用雌性恒河猴，其内源性促性腺激素 通过外科手术中断交流轴来终止分泌 下丘脑和脑下垂体之间 月经周期是 在这些动物中通过脉动注入合成的 促性腺激素释放激素（GnRH）。 有了这个模型系统， 循环LH的浓度可以通过改变 GnRH脉冲的频率和/或每次脉冲递送的GnRH量。 我们 将使用该模型系统来确定i）功能性黄体溶解是否 LH脉冲幅度不能增加， 在后一部分期间补偿LH脉冲频率的降低 的黄体期; ii）是否雌三醇和 孕酮促进黄体过早消退的结果是 LH脉冲频率和LH脉冲幅度两者的调制，以及iii） 内源性产生的雌二醇是否是黄体溶解素。 除了提供关于生理学的明确信息外， 调节灵长类动物体内黄体，获得的信息 这些研究可能会进一步加深我们对病理生理学的理解， 人类月经周期的紊乱，如黄体期过短 以及黄体期不足 最后，它越来越 显然，脉冲式GnRH治疗将广泛用于 治疗人类某些类型的闭经。 呈现的研究 在这一建议中可能提供有关 在促性腺激素释放激素驱动的月经周期中维持黄体， 这样做，可以直接指导临床内分泌学家在有效的 治疗人类不育症。

The long-term goal of this research is to elucidate the mechanism which causes the regression of the primate corpus luteum at the end of non-fertile menstrual cycles. The specific aim of the current proposal is to determine whether changes in the pattern of secretion of luteinizing hormone during the latter portion of the luteal phase is responsible for regression of the corpus luteum. These studies utilize female rhesus monkeys whose endogenous gonadotropin secretion is terminated by surgically interrupting the communication axis between the hypothalamus and pituitary gland. Menstrual cycles are restored in these animals by the pulsatile infusion of synthetic gonadotropin releasing hormone (GnRH). With this model system, the pattern of circulating LH can be controlled precisely by varying either the frequency of GnRH pulses and/or the amount of GnRH delivered per pulse. We will use this model system to determine i) whether functional luteolysis is the result of the inability of increases in LH pulse amplitude to compensate for reductions in LH pulse frequency during the latter portion of the luteal phase; ii) whether the synergestic actions of estragiol and progesterone in promoting premature luteal regression is the result of modulation of both LH pulse frequency and LH pulse amplitude, and iii) whether endogenously produced estradiol is a luteolysin. In addition to providing definitive information regarding the physiological regulation of the primate corpus luteum in vivo, the information gained from these studies may further our understanding of pathophysiological disturbances of the human menstrual cycle such as the short luteal phase and the inadequate luteal phase. Lastly, it is becoming increasingly apparent that pulsatile GnRH treatment will be used extensively in the treatment of certain types of amenorrhea in humans. The studies presented in this proposal may provide important information regarding the maintenance of the corpus luteum in GnRH-driven menstrual cycles and in doing so, may directly guide clinical endocrinologists in the effective treatment of infertility in humans.