The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system-the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man-comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment.

中文翻译：

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ACTH 和皮质醇分泌的动态及其对疾病的影响。


过去十年，我们对下丘脑-垂体-肾上腺 (HPA) 轴调节的理解取得了一些重大进展。稳态生理电路需要整合多种内部和外部刺激，并提供适合其目标组织响应参数的动态输出。 HPA 轴就是这种稳态系统的一个例子。最近的研究表明，该系统的主要输出（啮齿类动物的肾上腺糖皮质激素皮质酮和人类主要的皮质醇）的昼夜节律包括由于下丘脑下脉冲发生器而存在的不同幅度的脉冲。振荡的内源性糖皮质激素信号与轴的各个部分（包括肾上腺本身）内的调节系统相互作用，其中调节网络可以进一步改变激素的脉动释放。 HPA 轴输出采用动态振荡糖皮质激素信号的形式，需要在细胞水平上进行解码。如果通过施用长效合成糖皮质激素消除脉动信号，由此产生的生理调节破坏可能会对许多糖皮质激素依赖性身体系统产生负面影响。在慢性压力或某些疾病状态下，即使系统动态发生微妙的变化，也可能导致全身多个细胞和组织的功能输出发生变化，从而改变易感个体的代谢过程、行为、情感状态和认知功能。最近开发的一种新型时间疗法可以提供昼夜节律和超昼夜节律模式，为接受糖皮质激素治疗的患者带来了巨大的希望。