The hypothalamic-pituitary-adrenal axis: What can it tell us about stressors?
The hypothalamic-pituitary-adrenal axis: What can it tell us about stressors?
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DOI：
10.2174/187152706778559336
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发表时间：
2006-10-01
影响因子：
3
通讯作者：
Armario, Antonio
中科院分区：
文献类型：
--
作者：
Armario, Antonio
下丘脑-垂体-肾上腺（HPA）轴是一个非常敏感的生理系统，其激活，随之释放ACTH和糖皮质激素，是由广泛的心理体验和生理扰动（应激源）触发的。HPA轴也被大量结构和功能显著不同的药理学试剂激活，尽管在大多数情况下精确的机制仍然未知。HPA轴的激活是来自不同脑区的刺激输入会聚到下丘脑室旁核（PVN）的结果，在下丘脑室旁核中形成最重要的促ACTH分泌素（促肾上腺皮质激素释放因子，CRF和垂体后叶素-加压素，AVP）。血浆ACTH和皮质酮水平（后者在更受限制的条件下）被认为是良好的应激标志物，原因主要有三个：（a）它们的血浆水平与情绪和全身应激源的强度成比例，（B）每天重复暴露于应激源通常导致ACTH对相同应激源的反应降低，即所谓的适应或习惯化;以及（c）长期暴露于压力情况导致HPA轴的紧张性变化，其可用作这些情况的累积影响的指标。这些变化可以在静息条件下（即肾上腺重量、CRF和PVN中的AVP基因表达）或在作为经典内分泌学测试的一些挑战（施用CRF、ACTH或地塞米松）后进行评估。也有证据表明，HPA轴的激活也可能反映了压力情境特征的微妙变化（不可预测性，缺乏控制，预期奖励的遗漏，同种的存在），尽管这是一个需要进一步研究的主题。
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.