NEUROENDOCRINE MEDIATION OF SOCIALLY INDUCED ANOVULATION

社会诱发的无排卵的神经内分泌调节

• 批准号: 8172363
• 负责人: Mark E Wilson
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172363
• 关键词: Adult; Alleles; Animals; Anovulation; Behavioral; Brain region; Computer Retrieval of Information on Scientific Projects Database; Data; Eating; Energy Metabolism; Estradiol; Fatty acid glycerol esters; Feedback; Female; Fiber; Follow-Up Studies; Food; Funding; Genes; Genetic Polymorphism; Genotype; Grant; High Fiber Diet Low Fat; Housing; Hypersensitivity; Individual; Infertility; Institution; Intake; Length; Macaca mulatta; Measures; Mediation; Metabolic; Monkeys; Neurosecretory Systems; Outcome; Ovulation; Positron-Emission Tomography; Psychosocial Stress; Research; Research Personnel; Resources; Serotonin; Source; Stress; Testing; United States National Institutes of Health; Variant; Woman; adverse outcome; experience; insight; neuroimaging; promoter; receptor; reproductive; reuptake; social; treatment strategy

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 今年继续进行的研究评估了由于社会从属关系而产生的心理社会压力对成年雌性恒河猴的代谢、生殖和行为结果的影响。 此外，对编码5-羟色胺再摄取转运蛋白（5 HTT）的基因多态性的贡献进行了评估，因为其他研究表明，携带短启动子长度变体（s-变体）的一个或两个等位基因的个体比长启动子长度（l/l）纯合子的女性更容易受到心理社会压力的不良后果的影响。 在本年度，研究表明，生殖妥协所经历的下属女性是由于增强雌二醇负反馈抑制LH分泌。 事实上，这种超敏反应进一步增强下属女性与短启动子长度多态性（S-变体）是5 HTT基因。 后续研究表明，刺激排卵所必需的雌二醇的正反馈不受从属关系的影响。 这些数据表明，心理社会压力可能会增加不孕症的妇女的破坏机制负责卵泡成熟。 其他研究使用PET神经成像来测试假设，即在与应激反应相关的大脑区域中，从属S变异女性的GABA能受体亚型A会减少。 所有PET扫描均于2009年11月完成，分析正在进行中。 另外的研究使用自动喂食器来量化社会圈养雌性中标准低脂肪、高纤维猴子食物的摄入量，以更好地了解在下属中观察到的代谢缺陷。 在所有雌性动物中测量活动水平（作为能量消耗的替代指标）一周。 数据表明，下属，无论基因型，吃少的低脂肪，高纤维饮食比占主导地位的动物，并显示出类似的活动量。 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的能量。 这些研究为患有压力诱发的不孕症的妇女提供了可能的治疗策略。