Adrenal peripheral oscillator in generating the circadian glucocorticoid rhythm

The mammalian circadian timing system is organized into hierarchical structures with a central clock in the suprachiasmatic nucleus (SCN) and subsidiary peripheral oscillators. After the discovery of the local clockwork in peripheral organs and tissues, which have a molecular makeup similar to the central pacemaker SCN, uncovering the roles of the peripheral clock in the rhythmic physiology has been an emerging goal in chronobiology. Glucocorticoid (GC) is a multifunctional adrenal steroid hormone that shows a robust circadian rhythm. The daily GC rhythm has long been thought to be governed by the SCN via the hypothalamus-pituitary-adrenal neuroendocrine axis. Recent findings, however, indicate that multiple regulatory mechanisms, including the adrenal intrinsic mechanism by the peripheral clock, are also involved. GC regulates diverse physiological processes and acts as a signal for resetting peripheral clocks, which suggests the importance of the GC rhythm in harmonizing overall circadian physiology and behavior. Therefore, in this review, we will discuss the important role of the adrenal peripheral clockwork in the circadian regulation of GC and its physiological relevance in the circadian timing system.