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: 7562612
• 负责人: Mark E Wilson
• 金额: $ 3.16万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562612
• 关键词: Abdomen; Alleles; Anovulation; Body Weight; Body mass index; Caliber; Computer Retrieval of Information on Scientific Projects Database; Data; Female; Funding; Genes; Genetic Predisposition to Disease; Genotype; Grant; Height; Hormones; Hypothalamic structure; Institution; Insulin; Length; Leptin; Macaca mulatta; Measures; Mediation; Metabolic; Modeling; Monkeys; Neurosecretory Systems; Obesity; Phenotype; Research; Research Personnel; Resources; Score; Serotonin; Source; Supplementation; Testing; United States National Institutes of Health; Variant; hypothalamic-pituitary-adrenal axis; indexing; promoter; reproductive; reuptake; social

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. This project was initiated in July 2005 to study the neuroendocrine mechanisms and genetic vulnerability responsible for socially induced anovulation or functional hypothalamic anovulation using a female rhesus monkey model. Females were either homozygous for the longer promoter allele (l/l) for the gene that encodes the serotonin reuptake transporter (n = 20) or carried at least one of the short promoter length variants (l/s or s/s; n = 20). During the current year, we completed the assessment of the metabolic phenotype of females with different SERT genotypes. Females carrying the s allele, have lower body weights despite similar heights; have lower body mass index scores and smaller sagittal abdominal diameters as indices of adiposity; and have lower circulating levels of leptin and insulin. Following the completion of these assessments, females were removed from their natal groups to form 8 small groups of 5 monkeys each to test the hypothesis that females with the s allele will be responsive to the consequences of social subordination. Groups were formed so that all females were homogenous for the SERT genotype. That is, four groups were comprised entirely of l/l females and four groups were comprised entirely of females with at least one s allele. Data supported this hypothesis, as females with the s allele showed more metabolic deficits upon becoming subordinate than l/l females. In addition, subordinate females showed more activity within the limbic-hypothalamic-pituitary-adrenal axis and this was exacerbated in s variants females. Genotype had little effect on these measures in females attaining high dominance status. Ongoing studies are testing the hypothesis that supplementation with the metabolic hormone leptin will rescue the reproductive deficits shown in subordinate females, particularly those with the s allele in the SERT gene.

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。 该项目于2005年7月启动，使用雌性恒河猴模型研究社会诱导的无排卵或功能性下丘脑无排卵的神经内分泌机制和遗传脆弱性。 雌性动物是编码5-羟色胺再摄取转运蛋白基因的较长启动子等位基因（l/l）纯合子（n = 20）或携带至少一种短启动子长度变体（l/s或s/s; n = 20）。 在本年度，我们完成了不同SERT基因型女性代谢表型的评估。 携带s等位基因的女性，尽管身高相似，但体重较低;有较低的体重指数评分和较小的矢状腹部直径作为肥胖指数;瘦素和胰岛素的循环水平较低。 在完成这些评估后，将雌性从其纳塔尔组中取出，形成8个每组5只猴的小组，以检验具有s等位基因的雌性将对社会从属性的后果作出反应的假设。 形成组，使得所有雌性对于SERT基因型是同质的。 也就是说，四个组完全由1/1雌性组成，四个组完全由具有至少一个s等位基因的雌性组成。 数据支持这一假设，因为具有s等位基因的女性在成为下属时比l/l女性表现出更多的代谢缺陷。 此外，从属女性表现出更多的活动内的边缘-下丘脑-垂体-肾上腺轴，这是加剧了s变体的女性。 基因型对这些措施在女性达到高优势地位的影响不大。 正在进行的研究正在验证这样一种假设，即补充代谢激素瘦素将挽救从属女性的生殖缺陷，特别是那些在SERT基因中具有s等位基因的女性。