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

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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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:
NEUROENDOCRINE CONTROL OF OVARIAN DEVELOPMENT
卵巢发育的神经内分泌控制
  • 批准号:
    8357724
  • 财政年份:
    2011
  • 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:
NEURAL CONTROL OF THE PREPUBERTAL OVARY
青春期前卵巢的神经控制
  • 批准号:
    8357880
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
NEUROENDOCRINE CONTROL OF FEMALE PUBERTY
女性青春期的神经内分泌控制
  • 批准号:
    8357726
  • 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:
NEUROENDOCRINE CONTROL OF OVARIAN DEVELOPMENT
卵巢发育的神经内分泌控制
  • 批准号:
    8173170
  • 财政年份:
    2010
  • 资助金额:
    $ 5.82万
  • 项目类别:
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