MOLECULAR AND STRUCTURAL BASES OF HYPOTHALAMIC PUBERTY

下丘脑青春期的分子和结构基础

• 批准号: 7561967
• 负责人: Sergio R Ojeda
• 金额: $ 7.59万
• 依托单位: OREGON HEALTH & SCIENCE 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/7561967
• 关键词: Adolescent; Computer Retrieval of Information on Scientific Projects Database; Development; Feedback; Funding; Gene Expression; Genes; Grant; Human; Hypothalamic structure; Injection of therapeutic agent; Institution; KISS1R gene; Macaca mulatta; Modeling; Molecular; Monkeys; Phase; Physiological; Puberty; Research; Research Personnel; Resources; Signal Transduction; Source; Standards of Weights and Measures; Testicular Hormones; Time; United States National Institutes of Health; base; infancy; prevent

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 is a project aimed to understanding the physiological mechanisms responsible for the onset of puberty in humans. Studies performed in Dr. Ojeda's lab are those proposed under Specific Aim 3 of the main application. Aim 3: To determine, in the absence of interfering testicular hormone feedback, the global profile of hypothalamic gene expression at the time of 1) the suppression of pulsatile GnRH release during infancy, and 2) the resurgence in pulsatile GnRH release at the end of the juvenile phase of development. The rhesus monkey will be used as an experimental paradigm. Standard physiological models will be used to examine whether increased GPR54 signaling will sustain precocious GnRH release. Structural remodeling will be prevented by intrahypothalamic injection of endoneurominidase, and candidate and global gene expression will be examined by RNAse protection and hybridization to gene arrays containing 8,400 human cDNAs (or 8,000-10,000 monkey cDNAs), respectively.

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。 这是一个旨在了解人类青春期开始的生理机制的项目。 在Ojeda博士的实验室进行的研究是在主要申请的具体目标3下提出的研究。 目标三：在不存在干扰睾丸激素反馈的情况下，确定1）婴儿期脉冲式GnRH释放抑制和2）发育幼年期结束时脉冲式GnRH释放复苏时下丘脑基因表达的总体特征。 恒河猴将被用作实验范例。 将使用标准生理模型来检查GPR 54信号的增加是否会维持GnRH的早熟释放。 将通过下丘脑内注射神经内氨酸酶来防止结构重塑，并将通过RNA酶保护和分别与含有8，400个人cDNA（或8，000 - 10，000个猴cDNA）的基因阵列杂交来检查候选基因和全局基因表达。