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）：拟议的研究将探索 盐皮质激素受体（MR）在调节中的潜在作用 压力条件下的下丘脑-垂体-肾上腺轴（HPA）。健康促进协会 当有机体处于 面临压力时，在非压力时分泌低水平的 CORT 州。为了防止轴过度活动，CORT 负反馈 限制了这种激素系统的运作。负反馈的调节是通过 CORT 有两种受体：糖皮质激素受体 (GR) 和 MR。传统上， GR 被认为可以在应激反应期间控制 HPA，而 MR 则被认为可以控制 HPA。 将 HPA 控制在无压力的基础状态。然而，MR 的作用也可能是 是在压力情况下调节 HPA。 MR 的作用可能尤其重要 在轻度压力下很重要。例如人们每天面临的挑战。 如果 MR 由于经验性或先天性而无法正常运作 效应，生物体可能表现出对压力的 HPA 反应增强。异常HPA 功能与抑郁症、创伤后应激障碍和其他精神病理学有关。 因此，更好地了解 MR 在 HPA 控制中的作用非常重要。到 要实现这一目标，将确定一系列压力源，其中 HPA 需要 MR 来正常控制 CORT 反应。这将实现 通过用 MR 拮抗剂（例如 RU28318）治疗动物，然后 观察他们对压力的 CORT、ACTH 和 CRH 反应。然后，互动 MR 和 GR 对 HPA 的控制之间的关系将在以下几个压力源中进行检查 不同的强度。这样做是为了更好地理解的确切性质 MR 对压力期间 HPA 控制的贡献。最后，角色 压力源消除后，将检查控制 HPA 反应的 MR 反复经历过，以前表明这种情况会增加数量 大脑先生。