NEUROENDOCRINOLOGY OF PUBERTY AND SEXUAL DEVELOPMENT
青春期和性发育的神经内分泌学
基本信息
- 批准号:8357881
- 负责人:
- 金额:$ 5.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-05-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:AstrocytesCell Signaling ProcessCellsCommunicationEpidermal Growth Factor ReceptorErbB4 geneExcitatory Amino AcidsFemaleFundingGenesGlutamatesGoalsGrantHypothalamic structureIntercellular Adhesion MoleculesLigandsMediatingMetalloproteasesMusNational Center for Research ResourcesNeuroendocrinologyNeurogliaNeuronsNeurosecretory SystemsPathway interactionsPrimatesPrincipal InvestigatorProcessPubertyReceptor Protein-Tyrosine KinasesRegulator GenesResearchResearch InfrastructureResourcesSexual DevelopmentSignaling MoleculeSourceSystemTestingTimeTranscriptional RegulationUnited States National Institutes of Healthcosthomeodomainintercellular communicationnovelreceptor
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
This is a revised renewal application aimed at elucidating the neuroendocrine
mechanisms underlying the initiation of female puberty. During the last funding
period we examined the hypothesis that the activation of LHRH secretion at puberty
requires a cell-cell communication process provided by structurally and functionally
connected neuronal and glial subsets of the hypothalamus. We also began testing
the hypothesis that neuron-glia bidirectional communication, and hence the pubertal
process itself, is under the transcriptional control of "upstream" regulatory genes.
We established the initial framework supporting both concepts by: a) defining erbB-1
and erbB-4 tyrosine kinase receptors as major components of the communication
pathway used by glial cells to facilitate LHRH release, b) identifying
ionotropic/metabotropic receptors as signaling molecules used by glutamatergic
neurons to coordinate the facilitatory transsynaptic and glial input to LHRH neurons,
and c) defining the homeodomain gene TTF-1 as an example of an upstream
hierarchy of genes involved in the transcriptional control of puberty. In addition to
accomplishing these goals we identified two new components of the cell-cell signaling
process underlying erbB receptor-mediated glia-neuron bidirectional communication,
and discovered a novel gene that might represent a second upstream component of
the hypothalamic regulatory network controlling female sexual development. We now
propose studies to define the importance of these newly discovered systems in
neuroendocrine glia-neuronal communication and the impact they may exert on the
initiation of female puberty. To this end, the following aims are proposed: 1) To test
the hypothesis that TACE, a metalloproteinase involved in the ectodomain cleavage
of erbB ligands and erbB receptors, is required for excitatory amino acids to induce
glial TGFa release, and thus it is important for the neuron-glia mediated control of
puberty. 2) To test the hypothesis that glial expression of SynCAM, an intercellular
adhesion molecule found at reduced levels in astrocytes of erbB-4-deficient mice, is
involved in the glial-neuron control of female puberty. 3) To test the hypothesis that
TTF-1, a homeodomain gene required for the normal timing of female puberty, is an
upstream coordinator of the glial-neuronal interactions underlying the pubertal
activation of LHRH secretion. 4) To examine the hypothesis that a novel gene, termed
EAP-1 (Enhanced At. Puberty-1) belongs - along with TTF-1 - to the hierarchy of
controlling genes involved in the transcriptional regulation of the pubertal process.
这个子项目是利用资源的许多研究子项目之一。
由NIH/NCRR资助的中心拨款提供。对子项目的主要支持
子项目的首席调查员可能是由其他来源提供的,
包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能
表示该子项目使用的中心基础设施的估计数量,
不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。
这是一个修订后的更新申请,旨在阐明神经内分泌。
女性青春期启动的潜在机制。在上一次资助期间
期间,我们检验了青春期LHRH分泌激活的假设
需要从结构和功能上提供的信元间通信过程
下丘脑的神经元和神经胶质细胞亚群相连。我们也开始测试
神经元-神经胶质双向通讯的假说,因此青春期
过程本身,是在“上游”调控基因的转录控制之下。
我们通过以下方式建立了支持这两个概念的初始框架:a)定义erbB-1
和erbB-4酪氨酸激酶受体作为通讯的主要组成部分
神经胶质细胞促进LHRH释放的途径,b)识别
谷氨酸能受体作为信号分子的亲离子/代谢性受体
以协调LHRH神经元的易化性跨突触和神经胶质输入,
以及c)将同源结构域基因TTF-1定义为上游
参与青春期转录控制的基因层级。除了……之外
为了实现这些目标,我们确定了细胞的两个新组件-细胞信号
Erb受体介导的胶质细胞-神经元双向通讯的潜在过程,
并发现了一种新的基因,它可能代表了
控制女性性发育的下丘脑调节网络。我们现在
建议进行研究,以确定这些新发现的系统在
神经内分泌-神经胶质细胞-神经元通讯及其对脑损伤的影响
女性青春期的开始。为此,提出了以下目标:1)测试
金属蛋白酶TACE参与胞外结构域切割的假说
在erbB配体和erbB受体之间,是兴奋性氨基酸诱导
胶质细胞TGFa的释放,对神经元-胶质细胞介导的血管紧张素转换酶的调控具有重要意义。
青春期。2)检验一种细胞间质SynCAM的神经胶质表达
在erbB-4缺陷小鼠星形胶质细胞中发现的黏附分子水平降低,是
参与女性青春期的神经胶质细胞控制。3)检验假设
TTF-1是女性青春期正常发育所必需的同源结构域基因,是一种
青春期下神经胶质-神经元相互作用的上游协调器
激活LHRH分泌。4)检验一种新的基因,称为
EAP-1(增强版青春期-1)与TTF-1一起属于
参与青春期过程转录调控的控制基因。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Sergio R Ojeda其他文献
Sergio R Ojeda的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Sergio R Ojeda', 18)}}的其他基金
Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine Brain
通过将 RNAi 系统性递送至神经内分泌脑来改变能量平衡
- 批准号:
8539523 - 财政年份:2012
- 资助金额:
$ 5.82万 - 项目类别:
Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine Brain
通过将 RNAi 系统性递送至神经内分泌脑来改变能量平衡
- 批准号:
8427058 - 财政年份:2012
- 资助金额:
$ 5.82万 - 项目类别:
NOVEL MECHANISMS UNDERLYING THE TRANSSYNAPTIC CONTROL OF LHRH RELEASE
LHRH 释放的跨突触控制的新机制
- 批准号:
8357725 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
MOLECULAR AND STRUCTURAL BASES OF HYPOTHALAMIC PUBERTY
下丘脑青春期的分子和结构基础
- 批准号:
8357754 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
RNA INTERFERENCE THERAPY FOR HUNTINGTON'S DISEASE: STUDIES IN NON-HUMAN PRIMATES
亨廷顿病的 RNA 干扰疗法:在非人类灵长类动物中的研究
- 批准号:
8357819 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
INTRODUCING STABLE INFERTILITY BY RNA INTERFERENCE
通过 RNA 干扰引入稳定的不孕症
- 批准号:
8357818 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别: