Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response.
Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response.
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DOI：
10.1002/cphy.c150015
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发表时间：
2016-03-15
影响因子：
5.8
通讯作者：
Myers B
中科院分区：
文献类型：
--
作者：
Herman JP;McKlveen JM;Ghosal S;Kopp B;Wulsin A;Makinson R;Scheimann J;Myers B
下丘脑-垂体-肾上腺皮质（HPA 轴）是压力适应所必需的。 HPA 轴的激活会导致糖皮质激素的分泌，糖皮质激素作用于多个器官系统，重新调整能量资源以满足实际或预期的需求。 HPA 应激反应主要由神经机制驱动，调用下丘脑室旁核 (PVN) 神经元释放促肾上腺皮质激素释放激素 (CRH)。激活 CRH 释放的途径是应激源依赖性的：对稳态破坏的反应性反应经常涉及通过感觉中继对 PVN 神经元的直接去甲肾上腺素能或肽能驱动，而预期反应则使用源自上游边缘结构的寡突触途径。预期反应主要是由去抑制驱动的，去抑制是通过杏仁核中的 GABA 神经元对强直性 PVN 抑制的跨突触沉默来介导的。压力反应受到负反馈机制的抑制，糖皮质激素通过负反馈机制发挥作用，减少驱动力（脑干），促进边缘结构（例如海马体）的跨突触抑制。糖皮质激素还作用于 PVN，通过膜糖皮质激素受体快速抑制 CRH 神经元活性。慢性压力诱导的 HPA 轴激活有多种形式（慢性基础分泌过多、应激反应敏感，甚至肾上腺衰竭），其表现取决于压力源的长期性、强度、频率和方式等因素。驱动慢性应激反应的神经机制可能与控制急性反应的神经机制不同，包括招募新的边缘系统、下丘脑和脑干回路。重要的是，一个人对急性或慢性压力的反应是由许多因素决定的，包括遗传、早期生活经历、环境条件、性别和年龄。压力源发生的环境将决定一个人的急性或慢性压力反应是适应性的还是适应不良的（病理性的）。
The hypothalamo-pituitary-adrenocortical (HPA axis) is required for stress adaptation. Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand. The HPA stress response is driven primarily by neural mechanisms, invoking corticotrophin releasing hormone (CRH) release from hypothalamic paraventricular nucleus (PVN) neurons. Pathways activating CRH release are stressor dependent: reactive responses to homeostatic disruption frequently involve direct noradrenergic or peptidergic drive of PVN neurons by sensory relays, whereas anticipatory responses use oligosynaptic pathways originating in upstream limbic structures. Anticipatory responses are driven largely by disinhibition, mediated by trans-synaptic silencing of tonic PVN inhibition via GABAergic neurons in the amygdala. Stress responses are inhibited by negative feedback mechanisms, whereby glucocorticoids act to diminish drive (brainstem), promote trans-synaptic inhibition by limbic structures (e.g, hippocampus). Glucocorticoids also act at the PVN to rapidly inhibit CRH neuronal activity via membrane glucocorticoid receptors. Chronic stress-induced activation of the HPA axis takes many forms (chronic basal hypersecretion, sensitized stress responses, even adrenal exhaustion), with manifestation dependent upon factors such as stressor chronicity, intensity, frequency and modality. Neural mechanisms driving chronic stress responses can be distinct from those controlling acute reactions, including recruitment of novel limbic, hypothalamic and brainstem circuits. Importantly, an individual’s response to acute or chronic stress is determined by numerous factors, including genetics, early life experience, environmental conditions, sex and age. The context in which stressors occur will determine whether an individual’s acute or chronic stress responses are adaptive or maladaptive (pathological).