POSSIBLE ROLE OF NPY IN REPRODUCTIVE NEUROENDOCRINOLOGY

NPY 在生殖神经内分泌学中的可能作用

• 批准号: 3073372
• 负责人: JOHN K MC DONALD
• 金额: $ 5.27万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3073372
• 关键词: catecholamines; electrochemistry; estrus; high performance liquid chromatography; hormone binding protein; hormone regulation /control mechanism; laboratory rabbit; laboratory rat; luteinizing hormone; neuroendocrine system; neuropeptide Y; neuropeptides; radioimmunoassay; radiotracer

The long-term objective is to determine the role of Neuropeptide Y (NPY) in hypothalamic and hypophysial neuroendocrine control of luteinizing hormone (LH) secretion in the rat. The research addresses fundamental questions concerning NPY, which has been found in the rat and human brain in higher concentration than any peptide previously described and has been shown to affect LH and growth hormone (GH) secretion in vitro and in vivo. This research should yield important data about the role of NPY in basic neuroendocrine mechanisms which regulate reproductive hormone secretion. Aims: 1. Immunohistochemical methods will be used to precisely determine the anatomical relationships between NPY, luteinizing hormone releasing hormone (LHRH), and catecholamine (CA) containing cell bodies and terminals in the hypothalamus and pituitary gland. 2. Hypothalamic and pituitary homogenates will be examined for the presence of receptors which bind iodinated NPY in a saturable and reversible manner. 3. To examine the hypothesis that NPY influences LH release through effects on hypothalamic CAs and/or LHRH, hypothalamic fragments and slices will be perfused with medium containing NPY. The perfusate and tissue fragments will be collected and analyzed by RIA to measure the release of LHRH, and by HPLC with electrochemical detection to measure changes in CAs. 4. The direct effects of NPY on luteotrophs will be examined further using perfused columns of anterior pituitary cells exposed to NPY in the presence and absence of LHRH. 5. The potential sensitivity of hypothalamic NPY neurons to serum levels of gonadal steroids will be examined in female rats sacrificed at each stage of the estrous cycle and at specific times after ovariectomy and steroid replacement. Specific hypothalamic nuclei will be analyzed for changes in the concentrations of NPY and LHRH using RIA, and CAs using HPLC-EC. 6. The effects of these steroid manipulations on the sensitivity of the hypothalamus and pituitary to NPY administration (as described in aims 3 and 4 above) and on the density of NPY receptors in these tissues will be examined.

长期目标是确定神经肽Y（NPY）在 下丘脑和下生理神经内分泌控制曲叶激素的控制 （LH）大鼠分泌。 该研究解决了基本问题 关于npy，在较高的大鼠和人脑中发现了NPY 浓度比先前描述的任何肽都被证明 在体外和体内影响LH和生长激素（GH）分泌。 这 研究应产生有关NPY在基本中的作用的重要数据 调节生殖激素分泌的神经内分泌机制。 目的：1。免疫组织化学方法将用于精确确定 NPY，黄体生成激素释放之间的解剖学关系 激素（LHRH）和含有细胞体和末端的儿茶酚胺（CA） 在下丘脑和垂体中。 2。将检查下丘脑和垂体匀浆的存在 以可饱和和可逆的方式结合碘NPY的受体。 3。检验以下假设：NPY通过效应影响LH释放 在下丘脑CAS和/或LHRH上，下丘脑碎片和切片将是 用含有NPY的培养基灌注。 灌注液和组织碎片 RIA将收集和分析以测量LHRH的释放，并 通过与电化学检测的HPLC测量CAS的变化。 4。将使用NPY对黄质营养的直接影响进行进一步检查 在存在下暴露于NPY的前垂体细胞的灌注柱 和没有LHRH。 5。下丘脑NPY神经元对血清水平的潜在敏感性 性腺类固醇将在每个阶段牺牲的雌性大鼠中检查 发情周期以及卵巢切除术和类固醇后的特定时间 替代品。 将分析特定下丘脑核的变化 使用RIA的NPY和LHRH的浓度，以及使用HPLC-EC的CAS。 6。这些类固醇操纵对敏感性的影响 下丘脑和NPY给药的垂体（如AIM 3中所述 上面的4）以及这些组织中NPY受体的密度将是 检查。