SINGLE NUCLEOTIDE GENE POLYMORPHISMS AND FUNCTIONAL HYPOTHALAMIC AMENORRHEA

单核苷酸基因多态性与功能性下丘脑性闭经

• 批准号: 7958524
• 负责人: Sergio R Ojeda
• 金额: $ 5.02万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958524
• 关键词: Accounting; Adult; Affect; Age; Amenorrhea; Brain; Computer Retrieval of Information on Scientific Projects Database; DAXX gene; Defect; Disease; Female; Funding; Genes; Genetic Polymorphism; Genetic Variation; Grant; Hypothalamic structure; Institution; Modeling; Molecular; Neurons; Neurosecretory Systems; Nucleotides; Output; Periodicity; Pilot Projects; Play; Primates; Puberty; Reporting; Research; Research Personnel; Resources; Role; Single Nucleotide Polymorphism; Source; Testing; United States National Institutes of Health; Woman; functional hypothalamic amenorrhea; nonhuman primate; novel; reproductive; reproductive function

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. The objective of this Pilot project is to test the hypothesis that genetic variation in a novel gene termed EAP1 gene and/or one of its upstream controllers, manifested in the form of unique single nucleotide polymorphisms (SNPs), is a mechanism underlying the disorder of functional hypothalamic amenorrhea (FHA). The PI and his colleagues recently reported the functional characterization of this gene (termed EAP1, Enhanced at Puberty 1) and provided evidence supporting the concept that EAP1 is an upstream transcriptional regulator of neuronal networks controlling female reproductive function. These results also suggested that EAP1 plays an essential role in the control of female reproductive cyclicity. FHA is a disorder of the neuroendocrine brain that affects 3% of amenorrhea cases in women of reproductive age, and accounts for over 30% of all cases of amenorrhea. A natural nonhuman primate model of FHA exists in the ONPRC colony, with as many as 10% of adult females failing to cycle regularly or not cycling at all. The molecular underpinnings of this deficiency remain unknown, but they may be related to detrimental sequence defects in genes, such as EAP1, that control the rhythmic output of GnRH secretion from the hypothalamus.

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。 该试点项目的目的是验证这样的假设：称为EAP 1基因的新基因和/或其上游控制因子之一的遗传变异，以独特的单核苷酸多态性（SNP）的形式表现出来，是功能性下丘脑性闭经（FHA）的潜在机制。PI和他的同事最近报道了该基因的功能特征（称为EAP 1，在青春期1增强），并提供证据支持EAP 1是控制女性生殖功能的神经网络的上游转录调节因子的概念。这些结果也表明EAP 1在控制雌性生殖周期中起着重要作用。FHA是一种脑神经内分泌疾病，影响3%的育龄妇女闭经病例，占所有闭经病例的30%以上。在ONPRC群体中存在FHA的天然非人灵长类动物模型，其中多达10%的成年雌性无法定期骑自行车或根本不骑自行车。这种缺陷的分子基础仍然未知，但它们可能与基因中的有害序列缺陷有关，如EAP 1，该基因控制下丘脑GnRH分泌的节律性输出。