CATECHOLAMINES AND REPRODUCTIVE AGING

儿茶酚胺与生殖衰老

• 批准号: 3114297
• 负责人: JAMES W. SIMPKINS
• 金额: $ 14.02万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3114297
• 关键词: S adenosylmethionine; aging; animal colony; animal old age; animal puberty; blood; catecholamines; clonidine; dihydroxyphenylalanine; dissection; dopamine; estradiol; estrus; hypothalamus; luteinizing hormone; mature animal; median eminence; neurotransmitter biosynthesis; norepinephrine; ovariectomy; preoptic areas; progesterone; prolactin; radioimmunoassay; radiotracer; reproductive system; scintillation counter; sectioning; stainings; statistics /biometry; supraoptic nucleus; thin layer chromatography; tissue /cell preparation; tritium; tyrosine 3 monooxygenase

We propose to determine the role of age-related alterations in catecholamine (CA) and endogenous opioid peptide (EOP) neuronal systems in the initiation and maintenance of reproductive senescence in rats. We will also evaluate the role of age-related alterations in hormone secretion in the process of the aging of brain dopaminergic neurons. The proposed experiments will utilize young (3 to 4 months old), sexually mature rats; middle- aged (11-15 months old) rats which are either normally cycling or in the constant estrous (CE) state; and old (24-25 months old) CE rats of the Long Evans strain. We will evaluate LH pulses during the proestrous LH surge in middle-aged rats to determine the components of LH secretory dynamics which are altered just prior to the onset of the CE state. We will conduct similar evaluations of pulsatile LH release during the preovulatory surge of LH induced by clonidine in CE rats or by bromocriptine in repeatedly pseudopregnant rats. These studies will utilize frequent (every 5 min.) blood sampling of rats which are unanesthetized and unstressed. The role of chronic elevations in serum (E2) and prolactin (PRL) in the age-related decline in dopamine (DA) neuronal function will be evaluated. The dose-and time- dependency and the regional specificity of the effects of E2 and PRL on brain DA neurons would be determined. Also, the time- course of the recovery of DA neurons from the E2 on PRL insult will be determined. We have documented recently that chronic stimulation of opiate receptors cause a marked increase in the negative feedback effects of testosterone on LH secretion in males and in the negative and positive feedback effects of E2 in females. We would evaluate the role of EOP neuronal systems in the age-related increase in negative feedback sensitivity in males. These studies will utilize chronic exposure to the narcotic antagonist, naloxone, by a sustained-release pellet. Similar studies will be done using chronic morphine treatment in old CE rats and subsequent determination of the resulting changes in the effects of E2 on LH release. Finally, we have observed that a steroid-induced down-regulation of opioid receptors is involved in the series of neuronal events which generate the proestrous LH surge. Thus, we will evaluate the hypothesis that the age-related extinction of the preovulatory LH surge is a consequence of a deficit in this opioid-neuronal mechanism. Collectively, these studies will advance our knowledge of the neuronal and hormonal mechanism involved in the initiation and persistence of reproductive senescence.

我们建议确定年龄相关的改变在 内源性阿片肽（EOP）神经元 生殖系统的启动和维持 老鼠的衰老 我们还将评估与年龄相关的 衰老过程中激素分泌的改变 脑多巴胺能神经元。 拟议的实验将 利用年轻（3至4个月大），性成熟的大鼠; 老年（11-15个月大）大鼠，它们要么是正常的骑自行车，要么 处于持续发情（CE）状态;和老年（24-25月龄）CE Long Evans品系的大鼠。 我们将评估LH脉冲， 中年大鼠发情前期LH峰，以确定 LH分泌动力学的组成部分，这些组成部分在 到CE状态的开始。 我们将进行类似的评估 排卵前LH激增时LH的脉冲式释放 用可乐定或溴隐亭反复诱发CE大鼠 假孕大鼠 这些研究将使用频繁（每5 （最小值）未麻醉大鼠的血样采集， 没有压力 血清（E2）水平慢性升高， 催乳素（PRL）在与年龄相关的多巴胺（DA）下降 将评估神经元功能。 剂量和时间 依赖性和E2效应的区域特异性， 测定脑DA能神经元上的PRL。 另外，时间- PRL损伤后DA神经元从E2恢复的过程 将被确定。 我们最近的研究表明， 阿片受体的刺激会导致 睾酮对LH分泌的负反馈作用 男性和在负反馈和正反馈效应的E2在 女性 我们将评估EOP神经元系统的作用， 男性负反馈敏感度与年龄相关的增加。 这些研究将利用长期暴露于麻醉剂 拮抗剂，纳洛酮，通过缓释丸。 类似 将在旧CE中使用慢性吗啡治疗进行研究 大鼠和随后确定的结果变化， E2对LH释放的影响 最后，我们观察到， 类固醇诱导的阿片受体下调涉及 产生动情前期LH的一系列神经元活动 浪涌。 因此，我们将评估与年龄相关的假设， 排卵前LH峰的消失是 这种阿片类神经元机制的缺陷。 总的来说，这些 研究将推进我们对神经元和激素 参与的启动和持续的机制 生殖衰老