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.
这个子项目是利用这些资源的众多研究子项目之一
项目成果
期刊论文数量(0)
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专利数量(0)
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Sergio R Ojeda其他文献
Sergio R Ojeda的其他文献
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{{ 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:














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