Abstract：
Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive, catecholaminergic, and immunomodulation mechanisms, followed by a reset via cortisol. Stress system components, the sympathoadrenomedullary system, hypothalamic-pituitary-adrenal axis, and limbic structures are implicated in many chronic diseases by establishing an altered homeostatic state, allostasis. Consequent \"primary stress system disorders\" were popularly accepted, with phenotypes based on conditions such as Cushing syndrome, pheochromocytoma, and adrenal insufficiency. Cardiometabolic and major depressive disorders are candidates for hypercortisolemic etiology, contrasting the \"hypocortisolemic symptom triad\" of stress sensitivity, chronic fatigue, and pain. However, acceptance of chronic stress etiology requires cause-and-effect associations, and practical utility such as therapeutics altering stress system function. Inherent predispositions to stress system perturbations may be relevant. Glucocorticoid receptor (GR) variants have been associated with metabolic/neuropsychological states. The SERPINA6 gene encoding corticosteroid-binding globulin (CBG), was the sole genetic factor in a single-nucleotide variation-genome-wide association study linkage study of morning plasma cortisol, a risk factor for cardiovascular disease, with alterations in tissue-specific GR-related gene expression. Studies showed genetically predicted high cortisol concentrations are associated with hypertension and anxiety, and low CBG concentrations/binding affinity, with the hypocortisolemic triad. Acquired CBG deficiency in septic shock results in 3-fold higher mortality when hydrocortisone administration produces equivocal results, consistent with CBG\'s role in spatiotemporal cortisol delivery. We propose some stress system disorders result from constitutional stress system variants rather than stressors themselves. Altered CBG:cortisol buffering may influence interstitial cortisol ultradian surges leading to pathological tissue effects, an example of stress system variants contributing to stress-related disorders.
摘要：
Selye将压力描述为维持稳态的统一神经激素机制。急性应激系统激活是通过神经认知适应的，儿茶酚胺能,和免疫调节机制，然后通过皮质醇复位。应力系统组件,交感神经肾上腺髓系,下丘脑-垂体-肾上腺轴,边缘结构通过建立改变的体内平衡状态与许多慢性疾病有关，allostasis.随之而来的“原发性压力系统疾病”被普遍接受，基于库欣综合征等症状的表型，嗜铬细胞瘤,肾上腺功能不全.心脏代谢和重度抑郁症是皮质醇血症病因的候选者，对比压力敏感性的“皮质醇血症症状三联征”，慢性疲劳,和痛苦。然而,接受慢性应激病因需要因果关系，和实际效用，如改变应激系统功能的疗法。对应力系统扰动的固有倾向可能是相关的。糖皮质激素受体（GR）变体与代谢/神经心理状态有关。编码皮质类固醇结合球蛋白（CBG）的SERPINA6基因，是早晨血浆皮质醇的单核苷酸变异全基因组关联研究连锁研究中唯一的遗传因素，心血管疾病的危险因素，组织特异性GR相关基因表达发生改变。研究表明，基因预测的高皮质醇浓度与高血压和焦虑有关，和低CBG浓度/结合亲和力，低皮质醇三联征。当氢化可的松给药产生模棱两可的结果时，感染性休克的获得性CBG缺乏导致死亡率高3倍。与CBG在时空皮质醇传递中的作用一致。我们提出了一些压力系统疾病是由体质压力系统变体而不是压力源本身引起的。改变的CBG：皮质醇缓冲可能会影响间质皮质醇超激增，导致病理组织效应，应激系统变异导致应激相关疾病的一个例子。
