NEUROENDOCRINE MEDIATION OF SOCIALLY INDUCED ANOVULATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 今年的研究仍在继续，评估由社会从属关系引起的心理社会压力对成年雌性恒河猴代谢、生殖和行为结果的影响。 此外，还评估了编码5-羟色胺再摄取转运体(5HTT)基因的多态的贡献，因为其他研究表明，携带短启动子长度变异(S变异)的一个或两个等位基因的个体比携带长启动子长度纯合子的雌性个体(L/L)更容易受到心理社会压力的不利影响。 在这一年中，研究表明，下级雌性所经历的生殖妥协是由于雌二醇对促黄体生成素分泌的负反馈抑制增强。事实上，这种超敏反应在具有5HTT基因短启动子长度多态(S变种)的从属女性中进一步增强。后续研究表明，雌激素的正反馈对刺激排卵是必要的，不受从属关系的影响。 这些数据表明，心理社会应激可能通过破坏导致卵泡成熟的机制来增加女性的不孕症。其他研究使用正电子发射计算机断层扫描神经成像技术来验证以下假设，即在S基因突变的女性下属中，与应激反应相关的大脑区域中，GABA受体A亚型会减少。所有正电子发射计算机断层扫描已于2009年11月完成，分析工作正在进行中。其他研究使用自动喂食器来量化社交寄养雌性猴子的标准低脂肪、高纤维食物的摄入量，以更好地了解在下属身上观察到的代谢缺陷。活动水平，作为能量消耗的替代指标，对所有女性进行了为期一周的测量。 数据表明，无论是哪种基因，从属动物吃的低脂肪、高纤维食物比主要动物少，表现出相似的活动量。数据表明，与从属关系相关的低代谢状况是由于食物摄入量减少和每卡路里食物消耗更多能量所致。这些研究为患有应激性不孕症的女性提供了可能的治疗策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies have continued this year assessing the consequences of psychosocial stress, resulting from social subordination, on metabolic, reproductive, and behavioral outcomes in adult female rhesus monkeys. In addition, the contribution of polymorphisms in the gene that encodes the serotonin reuptake transporter (5HTT) was evaluated as other studies show individuals carrying one or both alleles of the short promoter length variant (s-variant) are more vulnerable to the adverse consequences of psychosocial stress than females homozygous for the long promoter length (l/l). During the current year, studies show that the reproductive compromise experienced by subordinate females is due to enhanced estradiol negative feedback inhibition of LH secretion. Indeed, this hypersensitivity was further enhanced in subordinate females with the short promoter length polymorphism (s-variant) is the 5HTT gene. Follow-up studies showed that positive feedback of estradiol, necessary to stimulate ovulation, is unaffected by subordination. These data indicate that psychosocial stress may increase infertility in women by disruption mechanisms responsible for follicular maturation. Other studies use PET neuroimaging to test the hypotheses that GABAergic receptor subtype A would be diminished in subordinate s-variant females in brain regions associated with stress reactivity. All PET scans were completed in Nov 2009 and analyses are underway. Additional studies used automated feeders to quantify intake of standard low fat, high fiber monkey chow in socially housed females to better understand the metabolic deficits observed in subordinates. Activity levels, as a surrogate measure of energy expenditure were measured for one week in all females. Data indicate that subordinates, regardless of genotype, eat less of the low fat, high fiber diet than dominant animals and show similar amounts of activity. The data indicate that the hypometabolic condition associated with subordination is due to reduced food intake and more energy expenditure per calorie of food consumed. These studies provide insights into possible treatment strategies for women suffering from stress-induced infertility.