Cooperative roles of the suprachiasmatic nucleus central clock and the adrenal clock in controlling circadian glucocorticoid rhythm

Abstract

The mammalian circadian timing system consists of the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and subsidiary peripheral clocks in other tissues. Glucocorticoids (GCs) are adrenal steroid hormones with widespread physiological effects that undergo daily oscillations. We previously demonstrated that the adrenal peripheral clock plays a pivotal role in circadian GC rhythm by driving cyclic GC biosynthesis. Here, we show that the daily rhythm in circulating GC levels is controlled by bimodal actions of central and adrenal clockwork. When mice were subjected to daytime restricted feeding to uncouple central and peripheral rhythms, adrenal GC contents and steroidogenic acute regulatory protein expression peaked around zeitgeber time 00 (ZT00), consistent with shifted adrenal clock gene expression. However, restricted feeding produced two distinct peaks in plasma GC levels: one related to adrenal GC content and the other around ZT12, which required an intact SCN. Light pulse-evoked activation of the SCN increased circulating GC levels in both wild-type and adrenal clock-disrupted mutant mice without marked induction of GC biosynthesis. In conclusion, we demonstrate that adrenal clock-dependent steroidogenesis and a SCN-driven central mechanism regulating GC release cooperate to produce daily circulatory GC rhythm.

Colonization with the commensal fungus Candida albicans perturbs the gut-brain axis through dysregulation of endocannabinoid signaling

“…3A Welch's t-test, p=0.0012). When the effect of circadian rhythm on serum CORT was examined, basal CORT in both groups was shown to increase over time throughout the afternoon, as expected (Chung et al, 2017) (Fig. 3B).…”

MECHANISMS IN ENDOCRINOLOGY: A sense of time of the glucocorticoid circadian clock: from the ontogeny to the diagnosis of Cushing’s syndrome

“…In addition, clock gene expression in the SCN, PVN and ARC responded to feeding schedules in a tissue-specific manner, despite on-going photoperiod zeitgeber (69). Recently, Chung et al (70) demonstrated that in mice, adrenal clockdependent steroidogenesis and the SCN-driven central mechanism regulating corticosterone release cooperate to produce a daily rhythm in circulating glucocorticoids. Taken together, these studies demonstrate that each component of the HPA axis has a distinctive circadian clock gene expression, although the main timing signals are propagated downstream from the SCN to the HPA axis.…”

The adrenal gland microenvironment in health, disease and during regeneration

“…24 Rhythmicity of daily GC pulses are tightly controlled by the coordinated action of a central master circadian clock, in the suprachiasmatic nucleus of the hypothalamus (SCN), and peripheral clock machinery, located in the adrenal gland, including canonical clock protein BMAl1. [25][26][27] While SCN controls the pulsatile secretion of two main regulators of adrenal steroidogenesis, namely, the corticotrophin-releasing hormone (CRH) and ACTH, production and secretion of adrenomedullary catecholamines is regulated by the sympathetic nervous system and splenic nerves. 28,29 Ample evidence supports the presence of bidirectional interactions between the adrenal cortex and the medulla.…”