Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor.
Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor.
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DOI：
10.1152/ajpendo.00521.2004
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发表时间：
2005-06
期刊：
影响因子：
--
通讯作者：
T. Pace;R. Spencer
中科院分区：
文献类型：
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作者：
T. Pace;R. Spencer
下丘脑-垂体-肾上腺（HPA）轴的糖皮质激素负反馈调节是由皮质类固醇受体介导的。人们普遍认为，在应激过程中，糖皮质激素受体（GR）对这种负反馈至关重要。相比之下，盐皮质激素受体（MR）与HPA轴调节基础，非应激条件。关于MR和GR在应激刺激过程中对HPA轴调节的相对作用的概念可能是不完整的。我们实验室最近的工作表明，以前估计的休息血浆皮质酮（CORT）水平的MR占用可能被高估。在应激源挑战过程中，可能有大量的MR可用于介导负反馈。我们推测，这可能是特别是在轻度应激挑战的情况下，当血浆CORT反应弱。在本研究中，首先用选择性MR拮抗剂RU 28318（50 mg/kg sc或500 ng/10 μ l（~ 1 μ.2 h（~ 1）icv））或溶剂（300 μ l丙二醇sc或10 μ l/2 h无菌盐水icv）全身或集中处理成年雄性Sprague-Dawley大鼠，然后用60 min新环境或束缚进行攻击。在载体对照中，束缚导致比新环境更大的血浆CORT反应。相对于媒介物对照，用RU 28318的全身和中枢治疗均显著增加了响应于新环境的CORT。然而，RU 28318治疗并没有增加CORT对束缚的反应。这些数据表明，MR可能是必要的糖皮质激素调节HPA轴活动在轻度应激，但不是在应激，导致更强大的CORT反应。
Glucocorticoid negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng.10 microl(-1).2 h(-1) icv) or vehicle (300 microl propylene glycol sc or 10 microl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.