Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes.
Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes.
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DOI：
10.3389/fendo.2014.00073
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发表时间：
2014
影响因子：
5.2
通讯作者：
Morris MJ
中科院分区：
文献类型：
--
作者：
Maniam J;Antoniadis C;Morris MJ
压力激活下丘脑-垂体-肾上腺（HPA）轴，然后调节适应程度和对后来的压力源的反应。众所周知，早期生活压力会影响以后的健康，但对早期生活压力如何损害HPA轴活动，导致压力反应系统的适应不良知之甚少。早期生活压力暴露（产前或产后早期）可能会影响发育途径，导致持久的结构和调节变化，易患成年期疾病。流行病学、临床和实验研究已经证明，早期生活压力产生对压力的长期高反应性，伴随着过度的循环糖皮质激素，以及增强的焦虑和抑郁样行为。最近，有证据表明，早期生活压力引起的代谢紊乱，例如高胰岛素血症和改变胰岛素敏感性暴露于高能量饮食在以后的生活。这使我们注意到后期环境对疾病脆弱性的贡献。早期生活压力可以改变外周组织中基因的表达，如糖皮质激素受体和11 β-羟基类固醇脱氢酶（11β-HSD 1）。我们认为HPA轴活性的改变和肝脏11β-HSD 1之间的相互作用调节了组织和循环糖皮质激素的可用性，并产生了不良的代谢后果。本文讨论了早年压力引起HPA轴适应不良的潜在机制，及其对能量利用和消耗的后续影响。积极的后期环境的影响，作为改善早期生活压力引起的健康赤字的一种手段，并提出机制支持早期生活压力和随后的有害环境暴露对代谢风险之间的相互作用。目前将早期生活压力与后期健康结果联系起来的方法的局限性也将得到解决。
Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be addressed.
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