Structural and Functional Evolution of Vertebrate Neuroendocrine Stress Systems
Structural and Functional Evolution of Vertebrate Neuroendocrine Stress Systems
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DOI：
10.1111/j.1749-6632.2009.04433.x
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Denver, Robert John
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文献类型：
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作者：
Denver, Robert John
脊椎动物下丘脑-垂体-肾上腺（HPA;或肾间）轴在动物发育以及对环境变化的生理和行为适应中起着关键作用。HPA或应力轴以分层的方式组织，反馈在沿轴的沿着几个点处操作。最近的研究结果表明，HPA轴的蛋白质，基因结构和信号通路存在于最早的脊椎动物中，并由于其关键的适应作用而被自然选择所保持。在所有研究的脊椎动物中，HPA轴在应激时被激活，并由促肾上腺皮质激素释放因子（CRF）家族的肽集中控制，其中已确定了四个旁系同源成员。CRF样肽的信号传导由至少两种不同的G蛋白偶联受体介导，并由分泌的结合蛋白调节。这些神经肽作为促垂体激素和神经递质/神经调质发挥作用，影响与压力相关的行为，如焦虑和恐惧。除了调节HPA活性和行为应激反应外，CRF样肽还涉及关键生命史转变的时间，例如两栖动物的变态和哺乳动物的出生。CRF样肽和信号传导组分也在中枢神经系统外表达，在中枢神经系统外它们具有不同的生理功能。糖皮质激素是HPA轴的下游效应物，在发育、能量平衡和行为中起重要作用，并对HPA轴的活性起反馈作用。
The vertebrate hypothalamus-pituitary-adrenal (HPA; or interrenal) axis plays pivotal roles in animal development and in physiological and behavioral adaptation to environmental change. The HPA, or stress axis, is organized in a hierarchical manner, with feedback operating at several points along the axis. Recent findings suggest that the proteins, gene structures, and signaling pathways of the HPA axis were present in the earliest vertebrates and have been maintained by natural selection owing to their critical adaptive roles. In all vertebrates studied, the HPA axis is activated in response to stressors and is controlled centrally by peptides of the corticotropin-releasing factor (CRF) family of which four paralogous members have been identified. Signaling by CRF-like peptides is mediated by at least two distinct G protein-coupled receptors and modulated by a secreted binding protein. These neuropeptides function as hypophysiotropins and as neurotransmitters/neuromodulators, influencing stress-related behaviors, such as anxiety and fear. In addition to modulating HPA activity and behavioral stress responses, CRF-like peptides are implicated in timing key life history transitions, such as metamorphosis in amphibians and birth in mammals. CRF-like peptides and signaling components are also expressed outside of the central nervous system where they have diverse physiological functions. Glucocorticoids are the downstream effectors of the HPA axis, playing essential roles in development, energy balance and behavior, and feedback actions on the activity of the HPA axis.