O'Connor T M, O'Halloran D J, Shanahan F
Department of Endocrinology and Medicine, Cork University Hospital and University College Cork, Cork, Ireland.
QJM. 2000 Jun;93(6):323-33. doi: 10.1093/qjmed/93.6.323.
Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.
生物体通过与环境保持平衡来生存。应激系统对这种内稳态至关重要。糖皮质激素通过改变基因表达、转录和翻译等多种途径，在分子水平上调节应激反应。其作用是抑制炎症细胞的功能，主要通过抑制细胞因子如白细胞介素 -1、白细胞介素 -6 和肿瘤坏死因子 -α 来介导。应激反应的核心效应器是促肾上腺皮质激素释放激素（CRH）和蓝斑 - 去甲肾上腺素（LC - NE）/交感神经系统。CRH 系统激活应激反应，并受到细胞因子、激素和神经递质的调节。糖皮质激素还调节生长、生殖和甲状腺轴。应激系统激活异常已在类风湿关节炎等炎症性疾病以及抑郁性抑郁症等行为综合征中得到证实。这些疾病与 CRH 系统基因异常的大鼠所出现的疾病相似。因此，应激反应是抵抗炎症和行为综合征的核心。在本综述中，我们描述了在分子、细胞、神经内分泌和行为水平对应激的反应，并讨论了这种反应失调导致的疾病过程以及它们治疗方面的最新进展。
