ADRENAL AXIS AND THE REPRODUCTIVE PROCESS

该提案的总体目标是调查相互作用 在两个主要的内分泌轴之间， 下丘脑-垂体-肾上腺(HPA)和 非人灵长类下丘脑-垂体-性腺(HPG)轴 模型，这是众所周知的雷赫斯猴子的相似性 人类在月经周期的控制方面。更多 具体来说，在前三个目标中，我们将通过以下方式研究这些机制 哪些应激刺激可能会干扰正常的生殖 进程。我们以前在卵巢切除(OVX)中的研究 猴子支持这一经典概念，即通过激活HPA来应对压力 和中枢HPA神经肽的释放，抑制脉动性 促性腺激素分泌。然而，这些研究也清楚地表明， 对压力的反应是由卵巢类固醇调节的。 因此，我们的前两个目标将比较 免疫/炎症性应激对促性腺激素释放的挑战 月经周期的不同阶段及其作用机制 区分急性反应和慢性反应。飞行员 研究表明，人们对压力的反应令人惊讶。 挑战在于，在特定的卵巢内分泌条件下 挑战变成了刺激而不是抑制 促性腺激素分泌。这些反应的长期影响 应对月经周期的压力挑战 调查过了。在目标3中，我们将研究HPA在 应激相关下丘脑闭经综合征的发生机制 并确定使用特定的拮抗剂是否可以激活 回归周期性。在最终目标中，我们将重点关注 HPA-HPG在卵泡期的相互作用 压力的影响。对用雌激素替代卵巢的猴子的初步研究表明 HPA在其未受刺激的状态下，可能会起到一个小但相关的作用 在支持紧张性促性腺激素分泌方面的作用。的关联性 这个卵泡发生的过程将在完好的猴子身上进行研究。 总体而言，这些数据将提供有关新机制的信息 HPA和胁迫通过这种方式影响生殖周期，并可能 提出新的治疗方法来解决……问题 下丘脑闭经。

The overall objective of the proposal is to investigate interactions between two major endocrine axes, the hypothalamo-pituitary-adrenal (HPA) and the hypothalamo-pituitary-gonald (HPG) axes in a non human primate model, the rehesus monkey, which is known for its similarity to the human in regard to the control of the menstrual cycle. More specifically in the first 3 aims, we will study the mechanisms by which stressful stimuli may interfer with the normal reproductive process. Our previous studies in the ovariectomized (OVX) monkey support the classical concept that stress, by activating HPA and the release of central HPA neuropeptides, suppresses pulsatile gonadotropin secretion. Yet, these studies also clearly indicate that the response to stress is modulated by the ovarian steroids. Thus, our first 2 aims will compare effects of an immune/inflammatory-like stress challenge on gonadotropin release at different stages of the menstrual cycle and the mechanisms which differentiate the acute and the chronic response. A pilot study has demonstrated surprising responses to the stress challenge, in that under specific ovarian endocrin conditions the challenge becomes stimulatory rather than inhibitory to gonadotropin secretion. The long term effects of these responses to the stress challenge on the menstrual cycle will then be investigated. In aim 3, we will examine the role of HPA in the genesis of the stress related hypothalamic amenorrhea syndrome and determine whether the use of specific antagonists may activate the return to cyclicity. In the final aim, we will focus on HPA-HPG interactions during the follicular phase, in the absence of stress. Pilot studies in OVX-estrogen replaced monkeys suggest that HPA, in its unstimulated state, may play a small but relevant role in support of tonic gonadotropin secretion. The relevance of this process to folliculogenesis will be studied in the intact monkey. Overall, the data will provide information about novel mechanisms by which HPA and stress influence themenstrual cycle and may suggest new therapeutical approaches to the problem of hypothalamic amenorrhea.