ROLE OF SEROTONIN IN MEDIATING STRESS-INDUCED INFERTILITY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这是一项新的授权，旨在探索5-羟色胺在调节应激诱导的不孕症中的作用。雌性食蟹猴和女性一样，全年有28天的月经周期，对压力的反应表现出个体差异，压力敏感型动物迅速发展为应激导致的生殖功能障碍，而具有压力弹性的动物在压力暴露期间保持正常的月经周期。这些研究中使用的压力是以功能性下丘脑闭经(FHA；一种临床症状，占女性不孕症的30%)女性为研究对象的模式，在这些患者中，猴子面临轻度心理压力(搬到新房间)和中度代谢压力(卡路里摄入量减少20%，每天适度跑步一小时，一周五天)。到目前为止，我们已经在非压力条件下对猴子进行了研究。我们发现，与更具应激适应能力的动物相比，应激敏感猴子的5-羟色胺生理性释放较低，中枢5-羟色胺能系统功能下调[色氨酸羟基酶(THP)2基因表达较低，5-羟色胺转运体(SERT)基因表达较少，5-HT-1A受体基因表达较少，5-羟色胺降解基因(MAO-A和MAO-B)表达较少]，下丘脑5HT2A和2C受体表达上调。我们有初步数据表明，在正常月经周期中，用5-羟色胺再摄取抑制剂(SSRI)治疗非应激条件下的应激敏感猴子会增加生殖激素的分泌。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This is a new grant to explore the role of serotonin in mediating stress induced infertility. Female cynomolgus monkeys, which like women, have 28-day menstrual cycles throughout the year, show individual differences in responsiveness to stress, with stress-sensitive animals rapidly developing stress-induced reproductive dysfunction, and stress-resilient animals maintaining normal menstrual cyclicity throughout stress exposure. The stress used for these studies is patterned after that documented in women with Functional Hypothalamic Amenorrhea (FHA; a clinical condition which accounts for as much as 30% of female infertility) in which monkeys are exposed to a mild psychological stress (moving to a new room) and a moderate metabolic stress (a 20% decrease in calorie intake and moderate running for an hour a day, 5 days a week). To date, we have studied monkeys in non-stressed conditions. We found that stress-sensitive monkeys have lower physiological release of serotonin, a down regulation of function in the central serotonergic system [as indicated by lower tryptophan hydroxylase (THP) 2 gene expression, less serotonin transporter (SERT) gene expression, less 5HT-1A receptor gene expression, and less expression of genes degrading serotonin (MAO-A and MAO-B)], as well as an up-regulation of 5HT2A and 2C receptors in the hypothalamus, compared to more stress-resilient animals. We have preliminary data showing that treatment of stress-sensitive monkeys in a nonstressed condition with a serotonin reuptake inhibitor (SSRI) increases reproductive hormone secretion in a normal menstrual cycle.