Estrogen regulation of channels involved in the control of energy homeostasis

雌激素对参与能量稳态控制的通道的调节

基本信息

  • 批准号:
    8323554
  • 负责人:
  • 金额:
    $ 23.84万
  • 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:
    2011-09-01 至 2014-05-31
  • 项目状态:
    已结题

项目摘要

The long range goal of this application is to understand the mechanisms by which estrogen and environmental estrogens affect hypothalamic functions such as energy homeostasis. There is an obesity epidemic in the US and understanding the etiology of any and all factors that contribute to expression of obesity is critical for treatment of this disorder. Therefore, the goal of the mentored projects is to understand how estradiol affects energy homeostasis through multiple membrane-initiated mechanisms that include the control of neuronal excitability through an estradiol-responsive membrane GPCR (mER) and control of gene expression in arcuate neurons through both ERa- and mER-mediated mechanisms. Estradiol is known to control energy homeostasis through ERa and mER because STX, a selective ligand for the mER, attenuates body weight gain post-ovariectomy. Estradiol also alters neuronal excitability of POMC arcuate neurons through the mER. One potential mER-mediated mechanism for the effects of estradiol is modulation of a non-inactivating, sub-threshold K+ current that tempers the excitability of POMC (M-current). To detennine if modulation of the M-current by estradiol plays a role in these effects, I will first measure the expression and activity of the KCNQ/M-current in POMC and NPY neurons from oil- and estradiol-treated females using qRT-PCR in pooled single cells and electrophysiology. Second, I will measure the effects of acute (via mER) estradiol treatment on the electrophysiological properties of the M-current in POMC and NPY neurons using whole cell patch recordings. The independent phase will build on the techniques learned during the mentored phase and examine the role of membrane-initiated and ERE-independent estrogen signaling in hypothalamic functions and determine whether environmental estrogens activate these same pathways in their effects. The first aim will determine the role of ERE-independent signaling in the control of energy homeostasis and hypothalamic gene regulation by estradiol and bisphenol A using wild-type, aERKO and ERalpha KI/KO mice models. The final aim will detennine the electrophysiological effects of bisphenol A on arcuate POMC and NPY neurons that control energy homeostasis.
这项应用的长期目标是了解雌激素和 环境雌激素影响下丘脑的功能,如能量动态平衡。有一个肥胖症 在美国流行,并了解任何和所有因素的病原学有助于表达 肥胖是治疗这种疾病的关键。因此,指导项目的目标是理解 雌激素如何通过多种膜启动机制影响能量动态平衡,包括 雌激素反应膜基因调控神经元兴奋性的研究 通过ERA和MER两种机制在弓状神经元中表达。已知雌二醇会 通过ERA和MER控制能量稳态,因为MER的选择性配体STX减弱 卵巢切除后体重增加。雌二醇也改变POMC弓状神经元的兴奋性 穿过梅尔河。雌激素作用的一个潜在的Mer介导的机制是调制 非失活,亚阈值K+电流,缓和POMC的兴奋性(M-电流)。以拘留九个如果 雌激素对M电流的调制在这些效应中起着作用,我将首先测量M电流的表达和 雌激素和油性激素对雌性POMC和NPY神经元KCNQ/M-电流的影响 单细胞聚合酶链式反应和电生理学。其次,我将衡量急性(通过MER)的影响 雌二醇对POMC和NPY神经元M-电流电生理特性的影响 全细胞贴片记录。独立阶段将建立在 指导阶段,并研究膜启动的和ERE非依赖的雌激素信号在 下丘脑的功能,并确定环境雌激素是否在 他们的影响。第一个目标将确定ERE非依赖信号在能量控制中的作用。 雌激素和双酚A对野生型AERKO和AERKO的动态平衡和下丘脑基因调控 ERAlpha Ki/KO小鼠模型。最终目的是确定双酚A对大鼠肾上腺皮质细胞的电生理效应。 弓形的POMC和NPY神经元控制能量平衡。

项目成果

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Troy Adam Roepke其他文献

Troy Adam Roepke的其他文献

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{{ truncateString('Troy Adam Roepke', 18)}}的其他基金

Sex differences in CRH signaling in the ovBNST underlie effects of chronic stressors
ovBNST 中 CRH 信号传导的性别差异是慢性应激源影响的基础
  • 批准号:
    10590639
  • 财政年份:
    2020
  • 资助金额:
    $ 23.84万
  • 项目类别:
Sex differences in CRH signaling in the ovBNST underlie effects of chronic stressors
ovBNST 中 CRH 信号传导的性别差异是慢性应激源影响的基础
  • 批准号:
    10030228
  • 财政年份:
    2020
  • 资助金额:
    $ 23.84万
  • 项目类别:
Sex differences in CRH signaling in the ovBNST underlie effects of chronic stressors
ovBNST 中 CRH 信号传导的性别差异是慢性应激源影响的基础
  • 批准号:
    10188648
  • 财政年份:
    2020
  • 资助金额:
    $ 23.84万
  • 项目类别:
Sex differences in CRH signaling in the ovBNST underlie effects of chronic stressors
ovBNST 中 CRH 信号传导的性别差异是慢性应激源影响的基础
  • 批准号:
    10366088
  • 财政年份:
    2020
  • 资助金额:
    $ 23.84万
  • 项目类别:
Sex differences in CRH signaling in the ovBNST underlie effects of chronic stressors
ovBNST 中 CRH 信号传导的性别差异是慢性应激源影响的基础
  • 批准号:
    10772793
  • 财政年份:
    2020
  • 资助金额:
    $ 23.84万
  • 项目类别:
Estrogen Regulation of Channels Involved in the Control of Energy Homeostatis
雌激素对参与能量稳态控制的通道的调节
  • 批准号:
    8678586
  • 财政年份:
    2014
  • 资助金额:
    $ 23.84万
  • 项目类别:
Estrogen regulation of channels involved in the control of energy homeostasis
雌激素对参与能量稳态控制的通道的调节
  • 批准号:
    8465757
  • 财政年份:
    2011
  • 资助金额:
    $ 23.84万
  • 项目类别:
Estrogen regulation of channels involved in the control of energy homeostasis
雌激素对参与能量稳态控制的通道的调节
  • 批准号:
    8235454
  • 财政年份:
    2011
  • 资助金额:
    $ 23.84万
  • 项目类别:
Estrogen regulation of channels involved in the control of energy homeostasis
雌激素对参与能量稳态控制的通道的调节
  • 批准号:
    7740663
  • 财政年份:
    2009
  • 资助金额:
    $ 23.84万
  • 项目类别:
The role of the M-current in the anorectic effects of estrogen and serotonin.
M 电流在雌激素和血清素的厌食作用中的作用。
  • 批准号:
    7329223
  • 财政年份:
    2007
  • 资助金额:
    $ 23.84万
  • 项目类别:

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