ROLE OF SEROTONIN IN MEDIATING STRESS-INDUCED INFERTILITY

血清素在缓解压力引起的不孕症中的作用

• 批准号: 8357841
• 负责人: CYNTHIA Louise BETHEA
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357841
• 关键词: Accounting; Animals; Clinical; Data; Down-Regulation; Female; Female infertility; Functional disorder; Funding; Gene Expression; Grant; Hour; Hypothalamic structure; Individual Differences; Infertility; Intake; Macaca fascicularis; Mediating; Menstrual cycle; Metabolic stress; Monkeys; Monoamine Oxidase A; Monoamine Oxidase B; National Center for Research Resources; Pattern; Periodicity; Physiological; Primates; Principal Investigator; Psychological Stress; Receptor Gene; Research; Research Infrastructure; Resources; Role; Running; Selective Serotonin Reuptake Inhibitor; Serotonin; Source; Stress; System; Tryptophan 5-monooxygenase; United States National Institutes of Health; Up-Regulation; Woman; cost; functional hypothalamic amenorrhea; receptor; reproductive; reproductive hormone; serotonin transporter

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 这是一项新的资助，旨在探索血清素在调节压力引起的不孕症中的作用。雌性食蟹猴与女性一样，全年有 28 天的月经周期，对压力的反应表现出个体差异，应激敏感的动物迅速出现应激引起的生殖功能障碍，而应激恢复性动物在整个应激过程中保持正常的月经周期接触。这些研究中使用的压力是根据患有功能性下丘脑闭经（FHA；一种临床病症，占女性不孕症的 30%）的女性记录的压力模式得出的，其中猴子受到轻微的心理压力（转移到新的环境）房间）和适度的代谢压力（卡路里摄入量减少 20%，每周 5 天、每天 1 小时适度跑步）。迄今为止，我们已经在无压力条件下研究了猴子。我们发现，应激敏感的猴子血清素的生理释放量较低，中枢血清素能系统的功能下调[如色氨酸羟化酶（THP）2基因表达较低、血清素转运蛋白（SERT）基因表达较少、5HT- 1A 受体基因表达，以及降解血清素的基因（MAO-A 和 MAO-B）表达减少]，以及与更具抗压能力的动物相比，下丘脑中的 5HT2A 和 2C 受体。我们的初步数据表明，在非应激条件下用血清素再摄取抑制剂（SSRI）治疗应激敏感的猴子可以增加正常月经周期中生殖激素的分泌。