BRAIN MONOAMINES AND LUTEINIZING HORMONE SECRETION
脑单胺和黄体生成素的分泌
基本信息
- 批准号:6387461
- 负责人:
- 金额:$ 19.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1979
- 资助国家:美国
- 起止时间:1979-12-01 至 2004-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The overall objective of this research program has been to identify and characterize the actions of the central neurotransmitter and neuropeptide systems that regulate the secretion of luteinizing hormone (LH) and prolactin (PRL) from the anterior pituitary gland in response to physiological stimuli. Studies conducted during the current funding period have demonstrated that one role of NPY in lactation is to amplify the inhibitory action of DA over PRL secretion, through a specific reduction in the entry of extracellular Ca2+ via L-type calcium channels. Because lactation is also characterized by a marked physiological hyperphagia, and because NPY is the most powerful central stimulant of feeding behavior, one set of proposed experiments will test the hypothesis that the NPY neurons of the arcuate nucleus also mediate the hyperphagia associated with lactation. Using a variety of approaches, the proposed experiments will investigate whether acute disruption of NPY transmission by central antiNPY immunoneutralization, antisense oligonucleotides or peptide antagonists of NPY decrease food intake during lactation and will test whether the Y1 and/or Y5 receptor mediates this action of NPY in lactation. A second major objective is to identify the physiological signal(s) responsible for the up-regulation of hypothalamic NPY during lactation. The proposed studies will test the hypothesis that the hypoinsulinemia associated with lactation increases the expression of NPY in the hypothalamus. These studies will test the effects of systemic insulin treatment of lactating rats on hypothalamic preproNPY mRNA levels, NPY peptide concentrations and NPY immunoreactivity, and will examine whether interruption of nursing, which reduces hypothalamic NPY expression, also alters circulating insulin concentrations. To test whether leptin might also be involved in the up-regulation of NPY in the arcuate-paraventricular-dorsomedial hypothalamic feeding network, a third set of studies will assess the effects of central leptin administration to lactating rats on hypothalamic pre proNPY mRNA levels, NPY tide concentrations and NPY immunoreactivity in the hypothalamus.
本研究计划的总体目标是确定和表征中枢神经递质和神经肽系统的作用,这些系统调节垂体前叶在生理刺激下黄体生成素(LH)和催乳素(PRL)的分泌。在当前资助期内进行的研究表明,NPY在泌乳中的一个作用是通过特异性减少细胞外钙离子通过l型钙通道进入来增强DA对PRL分泌的抑制作用。由于哺乳也以明显的生生性贪食为特征,并且由于NPY是摄食行为最强大的中枢刺激物,一组拟议的实验将验证弓形核的NPY神经元也介导与哺乳相关的贪食的假设。采用多种方法,本实验将研究NPY中枢抗免疫中和、反义寡核苷酸或NPY肽拮抗剂是否会在哺乳期间减少食物摄入量,并将测试Y1和/或Y5受体是否介导NPY在哺乳中的这种作用。第二个主要目的是确定哺乳期下丘脑NPY上调的生理信号。拟议的研究将验证与哺乳期相关的低胰岛素血症增加下丘脑NPY表达的假设。这些研究将测试泌乳大鼠全身胰岛素治疗对下丘脑preproNPY mRNA水平、NPY肽浓度和NPY免疫反应性的影响,并将研究中断护理是否会降低下丘脑NPY表达,也会改变循环胰岛素浓度。为了测试瘦素是否也可能参与下丘脑弓形-室旁-背内侧进食网络中NPY的上调,第三组研究将评估哺乳期大鼠中枢性瘦素给药对下丘脑前proNPY mRNA水平、NPY tide浓度和下丘脑NPY免疫反应性的影响。
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)
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WILLIAM R CROWLEY其他文献
WILLIAM R CROWLEY的其他文献
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{{ truncateString('WILLIAM R CROWLEY', 18)}}的其他基金
BRAIN MONOAMINES AND LUTEINIZING HORMONE SECRETION
脑单胺和黄体生成素的分泌
- 批准号:
6140485 - 财政年份:1999
- 资助金额:
$ 19.84万 - 项目类别:
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