CATECHOLAMINES AND REPRODUCTIVE AGING

这项赠款申请建议确定与年龄相关的 儿茶酚胺(CA)代谢在发育期和发育期的变化 维持大鼠生殖衰老。我们会进一步 广泛评估荷尔蒙变化的后果 与衰老有关的CA神经元的衰老速度。全 拟议的实验将利用年轻(3至4个月)、性成熟、 中年人(11至12个月)和老年人(22至24个月)不变 Long Evans品系的发情(CE)大鼠。在一些实验中， 雌性Fischer 344大鼠，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)和多巴胺(DA)在核团中的周转大幅下降。 黄体生成素丢失前的视结节前通路 在恒定发情期开始时，我们会评估 急性和长期给药对α-肾上腺素能和 多巴胺能受体激动剂对黄体生成素脉动性释放和类固醇诱导的影响 左撇子的涌动。这些治疗方法对黄体生成的影响 激素释放激素(LHRH)神经元将通过“推-拉”进行评估 插管法。慢性高催乳素血症(Hyp)在高血压中的作用 DA神经元的老化将通过测量下列序列来评估 高催乳素血症发病后多巴胺代谢的改变 表现出早期(Long-Evans大鼠)或晚期繁殖的动物 衰老。因此，DA神经元功能障碍的比率将与 与高血压的长度和/或严重程度有关，而不是年龄本身。平行 研究将评估慢性抑制血清的效果 催乳素对中老年CE大鼠DA代谢的影响角色 生殖中阿片类神经元的数量将通过以下方式进行评估： 脑啡肽和内啡肽在“推-拉”导管中的释放率 (Ii)评估慢性阻断对黄体生成素分泌能力的影响 阿片受体通过纳洛酮缓释微丸释放。最后， 慢性Hyp对衰老大鼠阿片类神经元功能的影响 使用类似的方法进行评估。这些研究将(I)推进我们的 对参与启动和持续的神经系统的知识 生殖衰老(II)提供了对其作用的初步评估 慢性荷尔蒙改变，与生殖衰老有关，在 测定CA神经元的衰老速率。

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.