Stress, hypercortisolism and corticosteroid receptors in depression: implicatons for therapy
Stress, hypercortisolism and corticosteroid receptors in depression: implicatons for therapy
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DOI：
10.1016/s0165-0327(00)00352-9
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发表时间：
2001-01-01
影响因子：
6.6
通讯作者：
Holsboer, F
中科院分区：
文献类型：
--
作者：
Holsboer, F
临床和临床前研究已经收集了大量证据表明，应激激素系统的改变在抑郁症的发展中起着重要的因果作用。在这篇综述文章中，对支持这一观点的研究进行了总结，并提供了一些数据，这些数据表明抑郁症与皮质类固醇受体功能受损有关，皮质类固醇受体功能受损导致神经激素过度释放，抑郁症的一些症状和体征可归因于此。下文提到的研究一致支持抗抑郁作用机制的概念，其作用超出生物胺的细胞膜受体，尤其包括改善皮质类固醇受体的功能。当被配体激活时，皮质类固醇受体作为转录因子，与许多已知的被抗抑郁药物激活的其他转录因子相对应。此外，还讨论了更直接干扰应激激素调节的药物的潜力，如皮质类固醇受体拮抗剂和促肾上腺皮质激素释放激素受体拮抗剂。(C)2001 Elsevier Science B.V.保留所有权利。
Clinical and preclinical studies have gathered substantial evidence that alterations of the stress hormone system play a major, causal role in the development of depression. In this review article, a summary of studies sustaining that view is given and data are presented which demonstrate that depression is associated with an impairment of corticosteroid receptor function that gives rise to an excessive release of neurohormones to which a number of signs and symptoms characteristic of depression can be attributed. The studies referred to in the following unanimously support the concept of an antidepressant mechanism of action that exerts its effects beyond the cell membrane receptors of biogenic amines and particularly includes the improvement of corticosteroid receptor function. When activated by ligands, corticosteroid receptors act as transcription factors in correspondence with numerous other transcription factors already known to be activated by antidepressants. Furthermore, the potential of drugs that interfere more directly with stress hormone regulation, such as corticosteroid receptor antagonists and corticotropin-releasing hormone receptor antagonists, is discussed. (C) 2001 Elsevier Science B.V. All rights reserved.