Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.
Mol Cell Endocrinol. 2012 Feb 5;349(1):20-9. doi: 10.1016/j.mce.2011.06.042. Epub 2011 Jul 18.
The pronounced daily variation in the release of adrenal hormones has been at the heart of the deciphering and understanding of the circadian timing system. Indeed, the first demonstration of an endocrine day/night rhythm was provided by Pincus (1943), by showing a daily pattern of 17-keto-steroid excretion in the urine of 7 healthy males. Twenty years later the adrenal gland was one of the very first organs to show, in vitro, that circadian rhythmicity was maintained. In the seventies, experimental manipulation of the daily corticosterone rhythm served as evidence for the identification of respectively the light- and food-entrainable oscillator. Another 20 years later the hypothalamo-pituitary-adrenal (HPA)-axis was key in furthering our understanding of the way in which rhythmic signals generated by the central pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) are forwarded to the rest of the brain and to the organism as a whole. To date, the adrenal gland is still of prime importance for understanding how the oscillations of clock genes in peripheral tissues result in functional rhythms of these tissues, whereas it has become even more evident that adrenal glucocorticoids are key in the resetting of the circadian system after a phase-shift. The HPA-axis thus still is an excellent model for studying the transmission of circadian information in the body.
肾上腺激素释放的明显日变化一直是解析和理解昼夜节律系统的核心。事实上，内分泌昼夜节律的第一个证明是由 Pincus（1943 年）提供的，他展示了 7 名健康男性尿液中 17-酮类固醇排泄的每日模式。20 年后，肾上腺是第一个在体外显示昼夜节律性的器官之一。在 70 年代，对皮质酮日节律的实验操作被用作分别识别光和食物可诱导振荡器的证据。又过了 20 年，下丘脑-垂体-肾上腺（HPA）轴在进一步理解由下丘脑视交叉上核（SCN）中的中央起搏器产生的节律信号如何传递到大脑的其他部位以及整个生物体方面发挥了关键作用。迄今为止，肾上腺对于理解外周组织中时钟基因的振荡如何导致这些组织的功能节律仍然至关重要，而肾上腺糖皮质激素在相位后重置昼夜节律系统方面的作用变得更加明显。因此，HPA 轴仍然是研究体内昼夜节律信息传递的绝佳模型。
