Armario Antonio
Institut de Neurociències and Unitat de Fisiologia Animal, Facultat de Ciències, Departament de Biologia Cel.lular, de Fisiologia i d'Inmunologia, Universitat Autònoma de Barcelona, Spain.
CNS Neurol Disord Drug Targets. 2006 Oct;5(5):485-501. doi: 10.2174/187152706778559336.
The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.
下丘脑-垂体-肾上腺（HPA）轴是一个极其敏感的生理系统，其激活以及随之而来的促肾上腺皮质激素（ACTH）和糖皮质激素的释放，是由多种心理体验和生理扰动（应激源）触发的。尽管在大多数情况下其确切机制尚不清楚，但大量结构和功能明显不同的药理剂也能激活HPA轴。HPA轴的激活是来自不同脑区的刺激输入汇聚到下丘脑室旁核（PVN）的结果，在PVN中形成了最重要的促肾上腺皮质激素分泌因子（促肾上腺皮质激素释放因子，CRF，和精氨酸加压素，AVP）。ACTH和皮质酮（后者在更受限的条件下）的血浆水平被视为应激的良好标志物，主要有三个原因：（a）它们的血浆水平与情绪和全身性应激源的强度成正比；（b）每天反复暴露于应激源通常会导致ACTH对同一应激源的反应降低，这被称为适应或习惯化；（c）长期暴露于应激情况会导致HPA轴的持续性变化，这些变化可用作这些情况累积影响的指标。这些变化可以在静息条件下（即肾上腺重量、PVN中CRF和AVP基因表达）或在一些激发试验（给予CRF、ACTH或地塞米松）后进行评估，这些都是经典的内分泌学检测。也有证据表明，HPA轴的激活可能还反映了应激情况特征的细微变化（不可预测性、缺乏控制、预期奖励的缺失、同种个体的存在），尽管这是一个需要进一步研究的课题。
