Stress and the menstrual cycle: relevance of cycle quality in the short- and long-term response to a 5-day endotoxin challenge during the follicular phase in the rhesus monkey.
Stress and the menstrual cycle: relevance of cycle quality in the short- and long-term response to a 5-day endotoxin challenge during the follicular phase in the rhesus monkey.
复制标题
DOI：
10.1210/jcem.83.7.4926
复制
发表时间：
1998-07
期刊：
影响因子：
--
通讯作者：
E. Xiao;L. Xia-Zhang;A. Barth;J. Zhu;M. Ferin
中科院分区：
文献类型：
--
作者：
E. Xiao;L. Xia-Zhang;A. Barth;J. Zhu;M. Ferin
压力激活中枢和外周通路以抑制月经周期的观点已被广泛接受，但这种情况发生的最初过程尚未得到研究。本研究使用相关的非人类灵长类动物模型来记录卵泡期中度短期应激事件所造成的周期性内分泌效应。应激范例是通过施用细菌内毒素[脂多糖(LPS)]产生的为期5天的炎症/免疫样挑战，通过释放内源性细胞因子和其他介质，诱导类似于细菌感染的病理生理反应。从卵泡期第2-8天开始，每天两次静脉注射LPS，持续5天。压力挑战导致所有猴子的卵泡期显着延长。观察到两个不同的组。在第 1 组 (n = 5) 中，LPS 治疗周期中卵泡期的平均 (+/- SE) 长度显着增加，从对照周期 2 中的 10.2 +/- 0.2 天增加到 30.8 +/- 4.3 天（一只猴子有 4 个月的闭经间隔）。在第 2 组 (n = 5) 中，卵泡期的长度显着增加，但没有超过 LPS 治疗的持续时间（9.7 +/- 1.1 与 13.6 +/- 1.2）。第 1 组在 LPS 后雌二醇浓度显着下降（34.8 +/- 5.5 vs. 16.2 +/- 6.5 pg/mL），并且在攻击后仍然受到抑制。在第 2 组中，雌二醇水平在整个 5 天 LPS 治疗期间保持稳定（26.0 +/- 6.5 与 25.6 +/- 3.9）。与卵泡期相似阶段的对照值相比，LPS治疗期间的LH和FSH值大部分高于对照。根据每个组的不同，LPS 治疗会延迟雌二醇和促性腺激素的激增不同的时间长度。综合黄体孕酮浓度的显着差异表征了第 1 组和第 2 组的控制周期（第 1 组：36.5 +/- 1.5，第 2 组：47.5 +/- 2.6）。在第 1 组中，在治疗期间和两个 LPS 后周期中，LPS 对黄体孕酮没有进一步影响。相反，在第 2 组中，LPS 第 1 周期后的黄体黄体酮综合浓度显着降低（降至 36.0 +/- 4.4）。每天早上注射 LPS 后第 3 小时皮质醇显着增加，但反应幅度在 5 天期间下降。第一次注射 LPS 后第 3 小时，黄体酮显着增加，但在随后的 LPS 注射后保持不变。我们的数据表明，卵泡期期间为期 5 天的炎症样发作可以延迟卵泡发生，并且对于已经表现出微妙的周期性退化的个体，该过程的损害会加剧，表现为应激发作前黄体期黄体酮分泌减少的形式。在正常月经周期的个体中观察到长期内分泌影响，表现为第一个应激后周期黄体分泌活动减少，这表明黄体期不足可能代表应激事件对正常月经周期造成损害的第一阶段。
The notion that stress activates central and peripheral pathways to inhibit the menstrual cycle is well accepted, but the initial processes through which this occurs have not been investigated. This study uses a relevant nonhuman primate model to document the cyclic endocrine effects imposed by a moderate short-term stress episode in the follicular phase. The stress paradigm is a 5-day inflammatory/immune-like challenge produced by the administration of bacterial endotoxin [lipopolysaccharide (LPS)], which, through the release of endogenous cytokines and other mediators, induces a physiopathological response similar to a bacterial infection. LPS was administered iv twice daily for 5 days starting on days 2-8 of the follicular phase. The stress challenge resulted in a significant lengthening of the follicular phase in all monkeys. Two distinct groups were observed. In group 1 (n = 5), the mean (+/- SE) length of the follicular phase in the LPS-treated cycle was significantly increased, from 10.2 +/- 0.2 in control cycle 2 to 30.8 +/- 4.3 days (except in one monkey that had a 4-month amenorrheic interval). In group 2 (n = 5), the length of the follicular phase significantly increased but not to exceed the duration of the LPS treatment (9.7 +/- 1.1 vs. 13.6 +/- 1.2). Estradiol concentrations decreased significantly after LPS in group 1 (34.8 +/- 5.5 vs. 16.2 +/- 6.5 pg/mL) and remained suppressed after the challenge. In group 2, estradiol levels remained stationary throughout the 5-day LPS treatment (26.0 +/- 6.5 vs. 25.6 +/- 3.9). Compared with control values at a similar stage of the follicular phase, most LH and FSH values during LPS treatment were higher than controls. Estradiol and gonadotropin surges were delayed by LPS treatment for a varying length of time according to each grp. Significant differences in integrated luteal progesterone concentrations characterized control cycles of groups 1 and 2 (group 1: 36.5 +/- 1.5, group 2: 47.5 +/- 2.6). In group 1, there were no further effects of LPS on luteal progesterone during the treatment and two post-LPS cycles. In contrast, in group 2, integrated luteal progesterone concentrations were significantly decreased in post-LPS cycle 1 (to 36.0 +/- 4.4). Cortisol significantly increased at hour 3 after each morning LPS injection but the amplitude of the response decreased over the 5-day period. Progesterone increased significantly by hour 3 after the first LPS injection but remained unchanged after subsequent LPS administration. Our data demonstrate that a 5-day inflammatory-like episode during the follicular phase can delay folliculogenesis and that damage to this process is intensified in individuals who already demonstrate a subtle cyclic degradation, in the form of decreased progesterone secretion in the luteal phases preceding the stress episode. Long-term endocrine effects, in the form of decreased luteal secretory activity in the first poststress cycle, are observed in normally cycling individuals, suggesting that inadequacy of the luteal phase may represent the first stage in the damage that a stress episode can inflict upon the normal menstrual cycle.