PHYSIOLOGY OF THE PROLACTIN RELEASING PEPTIDES

催乳素释放肽的生理学

• 批准号: 6638706
• 负责人: Willis K. Samson
• 金额: $ 25.73万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638706
• 关键词: autonomic nervous system; brain mapping; cardiovascular function; dopamine; hormone regulation /control mechanism; laboratory rat; messenger RNA; neuroendocrine system; neuropeptides; neuroregulation; prolactin; prolactin releasing /inhibiting factor; stress

DESCRIPTION (applicant's abstract): The focus of this proposal is to determine the roles the recently described prolactin releasing peptides (PrRPs) may play in stress-induced elevations of prolactin secretion (neuroendocrine actions in pituitary gland and neuromodulatory actions in brain) and autonomic function (neuromodulator actions in brain). We hypothesize that the PrRPs produced in brain and pituitary gland are required for the normal neuroendocrine and cardiovascular responses to stress. Specifically we hypothesize that PrRPs, either produced locally in pituitary gland or delivered to the gland via either the portal or peripheral circulations, play a role in the secretion of prolactin from the gland during stress. Furthermore, we hypothesize that the elevation in sympathetic tone during stress depends upon the actions of brain-derived PrRPs and that removal of those peptides will compromise the animal's cardiovascular response to stress. We will address the following Specific Aims (Questions): 1) Will physical or anticipatory stress elevate circulating plasma levels of PrRP, tissue levels of the peptides (brain, pituitary, adrenal), or expression of the gene (mRNA levels) in brain, pituitary gland or adrenal medulla? 2) Are the PrRPs effective releasing factors in the setting of dopamine withdrawal (which occurs in stress)? 3) Will central administration of PrRP stimulate prolactin secretion in conscious animals? 4) Can the site of action of PrRP in brain be identified by site-specific injections? 5) Will compromise of endogenous PrRP alter the neuroendocrine and cardiovascular responses to stress? The studies described here are designed to further characterize the pharmacology and physiology of the PrRPs, which have been demonstrated to act in the pituitary as neuroendocrine factors and in brain as modulators of autonomic outflow. The ultimate goal is to determine their importance in the maintenance of normal endocrine and cardiovascular function, in particular during stress. These studies will also begin to examine a potentially novel confluence of endocrine and autonomic responses to stress and thereby provide insight into the coordinated responses of multiple organ systems to stress.

描述（申请人的摘要）：该提案的重点是确定 最近描述的催乳素释放肽（PRRP）的角色可能扮演 在压力引起的催乳素分泌升高中（神经内分泌作用 大脑和自主功能中的垂体和神经调节作用 （大脑中的神经调节剂作用）。我们假设PRRP在 正常的神经内分泌需要大脑和垂体腺 心血管对压力的反应。具体来说，我们假设该prrps， 要么在垂体中局部生产，要么通过任何一个传递到腺体 门户或外围循环，在分泌中发挥作用 压力期间从腺上催乳素。此外，我们假设 压力期间同情语气的高程取决于 大脑衍生的PRRP和去除这些肽将损害 动物对压力的心血管反应。我们将解决以下内容 具体目的（问题）：1）身体或预期压力会增加 循环血浆PRRP的水平，肽的组织水平（大脑， 脑垂体，肾上腺）或大脑中基因（mRNA水平）的表达， 垂体或肾上腺髓质？ 2）有效释放是PRRP 在多巴胺戒断的情况下（在压力下发生）的因素？ 3）会 PRRP的中央给药刺激有意识的催乳素分泌 动物？ 4）PRRP在大脑中的作用部位可以通过 特定地点注射？ 5）将妥协内源性PRRP改变 神经内分泌和心血管对压力的反应？描述的研究 这里旨在进一步表征 已被证明在垂体中作用为prrps 神经内分泌因素和大脑作为自主流出的调节剂。这 最终目标是确定其在维持正常状态中的重要性 内分泌和心血管功能，特别是在压力期间。这些 研究还将开始检查内分泌的潜在新型融合 以及对压力的自主反应，从而洞悉 多器官系统对压力的协调反应。