CATECHOLAMINES AND REPRODUCTIVE AGING

儿茶酚胺与生殖衰老

• 批准号: 3114299
• 负责人: JAMES W. SIMPKINS
• 金额: $ 10.79万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3114299
• 关键词: S adenosylmethionine; aging; animal colony; animal old age; animal puberty; blood; catecholamines; clonidine; dihydroxyphenylalanine; dissection; dopamine; estradiol; estrus; luteinizing hormone; mature animal; median eminence; neurotransmitter biosynthesis; norepinephrine; ovariectomy; progesterone; prolactin; radioimmunoassay; radiotracer; reproductive system; scintillation counter; sectioning; stainings; statistics /biometry; thin layer chromatography; tissue /cell preparation; tyrosine 3 monooxygenase

This grant application proposes to determine the role of age-related alterations in catecholamine (CA) metabolism in the initiation and maintenance of reproductive senescence in the rat. We would further extensively evaluate the consequences of the hormonal alterations associated with senescence on the rate of aging of CA neurons. All proposed experiments would utilize young (3 to 4 months), sexually mature, and middle-aged (11 to 12 months) and old (22 to 24 months) constant estrous (CE) rats of the Long Evans strain. For some experiments, the female Fischer 344 rat, which maintains a long reproductive life would be used for comparison. Based upon our observation that both norepinephrine (NE) and dopamine (DA) turnover decreases substantially in nuclei along the preoptico-tuberal pathway prior to the loss of luteinizing hormone (LH) secretory capacity at the onset of constant estrus, we would assess the effects of acutely and chronically administered alpha-adrenergic and dopaminergic receptor agonists on pulsatile LH release and steroid-induced surges of LH. The effects of these treatments on Luteinizing hormone-releasing hormone (LHRH) neurons would be evaluated by "push-pull" cannulae methods. The role of chronic hyperprolactinemia (Hyp) in the aging of DA neurons would be evaluated by measuring the sequence of alteration in DA metabolism following the onset of hyperprolactinemia in animals which exhibit early (Long-Evans rats) or late reproductive senescence. Thus, the rate of DA neuronal dysfunction would be correlated with length and/or severity of the Hyp, rather than age per se. Parallel studies would evaluate the effects of chronic suppression of serum prolactin (PRL) on DA metabolism in middle-aged and old CE rats. The role of opioid neurons in reproductive would be evaluated (i) by estimating release rates of enkephalins and endorphins using "push-pull" cannulae and (ii) assessing the effects on LH secretory capacity of chronic blockade of the opioid receptor through sustained release naloxone pellets. Finally, the effects of chronic Hyp on opioid neuronal function in aging rats would be evaluated using similar methods. These studies will (i) advance our knowledge of the neuronal system involved in the initiation and persistence of reproductive senescence (ii) provide an initial assessment of the role of chronic hormonal alteration, associated with reproductive senescence, in determining the rate of aging of CA neurons.

这项拨款申请建议确定年龄相关的作用， 在起始和结束时， 维持大鼠的生殖衰老。 我们将进一步 广泛评估荷尔蒙变化的后果 与衰老相关的CA神经元的老化速率。 所有 建议的实验将利用年轻的（3至4个月），性成熟， 中年（11至12个月）和老年（22至24个月） Long Evans品系的发情（CE）大鼠。 对于一些实验， 雌性Fischer 344大鼠，其保持较长的生殖寿命， 用于比较。 根据我们的观察去甲肾上腺素 (NE)并且多巴胺（DA）周转在核团中沿着 黄体生成素（LH）丢失前的视前-结节通路 在恒定发情期开始时的分泌能力，我们将评估 急性和慢性给予α-肾上腺素能和 多巴胺能受体激动剂对脉冲式LH释放和类固醇诱导的 LH激增。 这些处理对促黄体生成的影响 用“推拉”法评价LHRH神经元 插管法 慢性高催乳素血症（Hyp）在妊娠中的作用 DA神经元的老化将通过测量 高催乳素血症发生后DA代谢的改变 表现出早期（Long-Evans大鼠）或晚期生殖的动物 衰老 因此，DA神经元功能障碍的发生率与 与Hyp的长度和/或严重程度有关，而不是年龄本身。 平行 研究将评估长期抑制血清 催乳素（PRL）对中老年CE大鼠DA代谢的影响。 的作用 阿片类神经元在生殖将评估（i）通过估计 使用“推拉”插管的脑啡肽和内啡肽的释放速率， (ii)评估慢性阻断LH对LH分泌能力的影响 阿片受体通过缓释纳洛酮丸。 最后， 慢性Hyp对衰老大鼠阿片神经元功能的影响 使用类似的方法进行评估。 这些研究将（i）促进我们的 神经元系统的知识参与的启动和持久性 （二）初步评估生殖衰老的作用 与生殖衰老有关的慢性激素改变， 确定CA神经元的老化速率。