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: 3317199
• 负责人: JOHN K MC DONALD
• 金额: $ 9.66万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3317199
• 关键词: catecholamines; high performance liquid chromatography; hormone inhibitor; hormone regulation /control mechanism; luteinizing hormone; neuroendocrine system; peptides; radioimmunoassay; reproduction

Objectives: The long-term objectives are to explore the role of NPY in reproductive neuroendocrine processes in the rat by examining the following hypothesis: 1) that the observed effects of NPY to inhibit luteinizing hormone secretion (see Preliminary Studies) are mediated through effects on hypothalamic catecholamines and/or LHRH secretion and 2) hypothalamic NPY containing neurons are responsive to changes in gonadal steroids. The proposed research addresses fundamental questions concerning NPY, a peptide found in the rat and human brain in higher concentration than any peptide previously described and should yield important data about its involvement in reproductive neuroendocrine processes such as the control of LH secretion. Aims: 1. To precisely determine the anatomical relationships which may exist between NPY and LHRH or catecholamine containing cell bodies and terminals, antisera to NPY will be generated in rabbits and immunohistochemical methods will be used to investigate the distribution of labeled cell bodies and terminals in the hypothalamus and pituitary gland. Results will be compared with descriptions of LHRH and catecholaminergic neuronal cell bodies and terminals. 2. Hypothalamic and pituitary homogenates will be examined for the presence of receptors which will bind iodinated NPY in a saturable and reversible manner. 3. To examine the hypothesis that NPY inhibits LH release through effects on hypothalamic catecholamines and/or LHRH secretion, hypothalamic fragments and slices will be perfused with medium containing NPY. The perfusate and tissue fragments will be collected and analyzed by RIA and HPLC with ultraviolet and electrochemical detection for changes in LHRH and catecholamines. 4. Potential direct effects of NPY on luteotrophs will be determined using perfused columns of anterior pituitary cells exposed to NPY with or without LHRH. 5. To explore the hypothesis that hypothalamic NPY neurons are responsive to changes in serum levels of gonadal steroids, male and female rats will be sacrificed at various times after gonadectomy and steroid replacement. Regions of the hypothalamus will be analyzed for changes in the concentration of NPY using RIA and HPLC.

目标：长期目标是探索NPY在 大鼠的生殖神经内分泌过程通过检查以下 假设：1）观察到的NPY抑制黄体生成的作用 激素分泌（见初步研究）是通过对 下丘脑儿茶酚胺和/或LHRH分泌和2）下丘脑NPY 含有神经元对性腺类固醇的变化有反应。 这 拟议的研究解决了有关NPY的基本问题，肽 在大鼠和人脑中发现的浓度比任何肽都更高 先前描述的并应产生有关其参与的重要数据 在生殖神经内分泌过程中，例如控制LH 分泌。 目的：1。准确确定可能的解剖学关系 存在于NPY和LHRH或含有细胞体的Catecholamine之间，并且 终端，Antisera至NPY将在兔子中产生 免疫组织化学方法将用于研究 下丘脑和垂体中标记的细胞体和末端。 结果将与LHRH和Catecholamin能的描述进行比较 神经元细胞体和末端。 2。将检查下丘脑和垂体匀浆的存在 可在可饱和且可逆的碘化NPY结合的受体 方式。 3。检验以下假设：NPY通过效应抑制LH释放 关于下丘脑儿茶酚胺和/或LHRH分泌，下丘脑 碎片和切片将用含有NPY的培养基灌注。 这 RIA将收集和分析灌注液和组织碎片 HPLC具有紫外线和电化学检测，用于LHRH和LHRH的变化 儿茶酚胺。 4。将使用NPY对黄质营养的潜在直接影响。 灌注垂体前垂体细胞的灌注柱，无论是否有或没有 LHRH。 5。探讨下丘脑NPY神经元反应灵敏的假设 为了改变性腺类固醇水平，雄性和雌性大鼠将 雌性切除术和类固醇替代后的不同时间处死。 将分析下丘脑区域的变化 使用RIA和HPLC的NPY浓度。