Mineralocorticoid-R Control of HPA Stress Response

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 下丘脑-垂体-肾上腺轴（HPA）在应激条件下。自置居所津贴 分泌增加皮质醇或皮质酮（CORT）时，有机体是 面对压力，而在非压力期间分泌低水平的CORT states.防止轴的过度活动，CORT负反馈 限制了激素系统的运作负反馈是由 CORT的两种受体：糖皮质激素受体（GR）和MR。传统上， GR被认为在应激反应期间控制HPA，而MR被认为在应激反应期间控制HPA。 将HPA控制在非应激基础状态。然而，MR的作用也可能 在压力下调节HPA。MR的作用可能特别 在温和的压力下很重要。比如人们每天面临的挑战。 如果MR由于经验性或先天性原因而无法正常工作， 在这种情况下，生物体可能会对应激表现出增加的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理学有关。 因此，更好地理解MR在HPA控制中的作用是相关的。到 完成这一点，一系列的压力源将被确定，其中HPA 需要MR来正常控制CORT反应。这将是完成 通过用MR拮抗剂（例如，RU 28318），然后 观察他们对应激的CORT、ACTH和CRH反应。其次，互动 将在以下几种应激源中检查HPA的MR和GR控制之间的关系： 不同的强度。这样做是为了更好地了解 MR对压力期间HPA控制的贡献。最后， MR在控制HPA反应中的作用将在压力源被释放后进行检查。 反复经历，以前的情况表明，增加的数量， 脑MR

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.