SINGLE NUCLEOTIDE GENE POLYMORPHISMS AND FUNCTIONAL HYPOTHALAMIC AMENORRHEA

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。 这个试点项目的目的是验证这样一种假设，即一个被称为EAP1基因的新基因和/或其上游控制基因之一的遗传变异，表现为独特的单核苷酸多态(SNPs)，是功能性下丘脑闭经(FHA)疾病的一个机制。PI和他的同事们最近报道了该基因(称为EAP1，在青春期1岁时增强)的功能特征，并提供了证据，支持EAP1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。这些结果还表明，EAP1在控制雌性生殖周期性中起着重要作用。FHA是一种神经内分泌脑疾病，影响3%的育龄妇女闭经病例，占所有闭经病例的30%以上。ONPRC群体中存在一种自然的非人类灵长类动物模型，多达10%的成年雌性不定期骑自行车或根本不骑自行车。这种缺陷的分子基础尚不清楚，但它们可能与EAP1等基因的有害序列缺陷有关，EAP1控制着下丘脑GnRH分泌的节律性输出。

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.