ROLE OF SEROTONIN IN MEDIATING STRESS-INDUCED INFERTILITY

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这是一个新的赠款，探讨血清素的作用，在调解压力引起的不孕症。雌性食蟹猴和女性一样，一年中有28天的月经周期，对压力的反应存在个体差异，压力敏感的动物迅速发展为压力诱导的生殖功能障碍，而压力适应性动物在整个压力暴露过程中保持正常的月经周期。用于这些研究的压力模式是在患有功能性下丘脑闭经（FHA;一种占女性不孕症30%的临床病症）的女性中记录的，其中猴子暴露于轻度心理压力（搬到新房间）和中度代谢压力（卡路里摄入量减少20%，每周5天，每天适度跑步1小时）。到目前为止，我们已经研究了非应激条件下的猴子。我们发现，应激敏感的猴子具有较低的5-羟色胺生理释放，中枢神经系统功能的下调[如较低的色氨酸羟化酶（THP）2基因表达、较低的5-羟色胺转运体（SERT）基因表达、较低的5 HT-1A受体基因表达和较低的5-羟色胺降解基因表达所示（MAO-A和MAO-B）]，以及下丘脑中5 HT 2A和2C受体的上调，与更具应激弹性的动物相比。我们有初步的数据表明，在非应激条件下，用5-羟色胺再摄取抑制剂（SSRI）治疗应激敏感的猴子，可以增加正常月经周期中的生殖激素分泌。

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.