Mineralocorticoid-R Control of HPA Stress Response

盐皮质激素-R 对 HPA 应激反应的控制

• 批准号: 6528776
• 负责人: THADDEUS PACE
• 金额: $ 2.52万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-02 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6528776
• 关键词: adrenalectomy; adrenocorticotropic hormone; biofeedback; corticosteroid receptors; corticotropin releasing factor; depression; disease /disorder model; gene expression; hippocampus; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; immunocytochemistry; in situ hybridization; laboratory rat; neuroendocrine system; neuroregulation; posttraumatic stress disorder; protein protein interaction; protein structure function; radioimmunoassay; stress; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): The proposed research will explore the potential role of the mineralocorticoid receptor (MR) in the regulation of the hypothalamic-pituitary-adrenal axis (HPA) under conditions of stress. The HPA secretes increased cortisol or corticosterone (CORT) when an organism is confronted by stress, while secreting a low level of CORT during non-stress states. To prevent excessive activity of the axis, CORT negative feedback limits the operation of this hormone system. Negative feedback is mediated by two receptors for CORT: the glucocorticoid receptor (GR) and MR. Traditionally, GR is thought to control the HPA during a stress response and MR thought to control the HPA in non-stress, basal states. However, the role of MR might also be to regulate the HPA in stress situations. The role of MR may be especially important during milder stress. such as the challenges people face every day. If MR are not functioning properly because of experiential or congenital effects, an organism may show an increased HPA response to stress. Abnormal HPA function has been connected with depression, PTSD, and other psychopathologies. It is therefore relevant to better understand the role of MR in HPA control. To accomplish this, a range of stressor will be identified in which the HPA requires MR for normal control of the CORT response. This will be accomplished via treatment of animals with MR antagonists (e.g., RU28318), and then observing their CORT, ACTH, and CRH response to stress. Then, the interaction between MR and GR control of the HPA will be examined in several stressors of varying intensities. This will be done to better understand the exact nature of MR contribution to control of the HPA during stress. And finally, the role of MR in controlling HPA responding will be examined after a stressor has been experienced repeatedly, a situation previously shown to increase the number of brain MR.

描述(由申请人提供)：建议的研究将探索 盐皮质激素受体(MR)在调节血管紧张素转换酶活性中的作用 应激条件下的下丘脑-垂体-肾上腺轴(HPA)。自置居所津贴 分泌增加的皮质醇或皮质酮 面对应激，同时在非应激期间分泌低水平的皮质醇 各州。为防止轴过度活动，CORT负反馈 限制了这种荷尔蒙系统的运行。负面反馈是由 皮质醇的两种受体：糖皮质激素受体(GR)和MR传统上， GR被认为在应激反应中控制HPA，而MR认为 将HPA控制在非应激的基础状态。然而，可能先生的角色也 在有压力的情况下调节HPA。MR的作用可能特别是 在较温和的压力下很重要。比如人们每天面临的挑战。 如果MR由于经验或先天原因而不能正常工作 一个生物体可能会对压力表现出更高的HPA反应。HPA异常 功能与抑郁症、创伤后应激障碍和其他精神病态有关。 因此，更好地理解MR在HPA控制中的作用是相关的。至 要做到这一点，将确定一系列的应激源，其中HPA 需要MR才能正常控制CORT反应。这将会实现的 通过用MR拮抗剂(例如RU28318)治疗动物，然后 观察其皮质醇、促肾上腺皮质激素和促肾上腺皮质激素释放激素对应激的反应。然后，互动 在MR和GR之间对HPA的控制将在以下几个应激源中进行检查 不同的强度。这样做是为了更好地了解 MR在应激状态下对HPA控制的贡献。最后，这一角色是 控制HPA反应的MR将在压力源已经被 反复经历，这种情况以前显示出增加了 布莱恩先生。