Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
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DOI：
10.1016/s0022-3999(02)00429-4
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发表时间：
2002-10-01
影响因子：
4.7
通讯作者：
Chrousos, GP
中科院分区：
文献类型：
--
作者：
Tsigos, C;Chrousos, GP
压力系统协调有机体对任何类型的压力源的适应性反应。(1)应激系统的主要组成部分是促肾上腺皮质激素释放激素（CRH）和蓝斑-去甲肾上腺素（LC/NE）-自主神经系统及其外周效应器、垂体-肾上腺轴和自主神经系统的分支。应激系统的激活导致行为和外周变化，从而提高生物体调节体内平衡的能力并增加其生存机会。CRH和LC/NE系统刺激唤醒和注意力，以及中皮质边缘多巴胺能系统，其参与预期和奖励现象，以及下丘脑β-内啡肽系统，其抑制疼痛感觉，因此增加镇痛。CRH抑制食欲并通过儿茶酚胺能系统激活产热。此外，杏仁核和海马体与应激系统之间存在相互作用，应激系统刺激这些元素并受其调节。CRH在应激时抑制GnRH分泌中起重要作用，同时，通过生长抑素，它还抑制GH、TRH和TSH的分泌，从而抑制生殖、生长和甲状腺功能。有趣的是，这三种功能都接受并依赖于正性的儿茶酚能输入。另一方面，下丘脑-垂体-肾上腺（HPA）轴的终末激素糖皮质激素具有多种作用。它们同时抑制CRH、LCNE和β-内啡肽系统，并刺激中皮质边缘多巴胺能系统和杏仁核的CRH肽能中央核。此外，它们直接抑制垂体促性腺激素、GH和TSH分泌，使性类固醇和生长因子的靶组织对这些物质产生抗性，并抑制5'脱碘酶，该酶将相对无活性的四碘甲状腺原氨酸（T-4）转化为三碘甲状腺原氨酸（T-3），进一步抑制生殖、生长和甲状腺功能。它们对脂肪组织也有直接和胰岛素介导的影响，最终促进内脏肥胖、胰岛素抵抗、血脂异常和高血压（代谢综合征X），并对骨骼产生直接影响，引起“低转换”骨质疏松症。中枢CRH通过糖皮质激素和儿茶酚胺抑制炎症反应，而外周神经CRH直接分泌刺激局部炎症（免疫CRH）。CRH拮抗剂可用于与应激系统的慢性活动过度相关的人类病理状态，例如精神病性抑郁和慢性焦虑，沿着可预测的行为、神经内分泌、代谢和免疫变化，基于上述相互关系。相反地，CRH分泌/作用的增强剂可用于治疗非典型抑郁症、产后抑郁症和纤维肌痛/慢性疲劳综合征，所有这些都以低HPA轴和LCNE活性、疲劳、抑郁性疼痛、痛觉过敏和对刺激的免疫/炎症反应增加为特征。(C)2002年爱思唯尔科技有限公司All rights reserved.
The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1) The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholarninergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LCNE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T-4) to triiodothyronine (T-3) contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LCNE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli. (C) 2002 Elsevier Science Inc. All rights reserved.