Circadian rhythms and the HPA axis: A systems view

The circadian timing system comprises a network of time‐keeping clocks distributed across a living host whose responsibility is to allocate resources and distribute functions temporally to optimize fitness. The molecular structures generating these rhythms have evolved to accommodate the rotation of the earth in an attempt to primarily match the light/dark periods during the 24‐hr day. To maintain synchrony of timing across and within tissues, information from the central clock, located in the suprachiasmatic nucleus, is conveyed using systemic signals. Leading among those signals are endocrine hormones, and while the hypothalamic–pituitary–adrenal axis through the release of glucocorticoids is a major pacesetter. Interestingly, the fundamental units at the molecular and physiological scales that generate local and systemic signals share critical structural properties. These properties enable time‐keeping systems to generate rhythmic signals and allow them to adopt specific properties as they interact with each other and the external environment. The purpose of this review is to provide a broad overview of these structures, discuss their functional characteristics, and describe some of their fundamental properties as these related to health and disease. This article is categorized under: Immune System Diseases > Computational Models Immune System Diseases > Biomedical Engineering Signals from the SCN entrain the endocrine system driving the production of endocrine hormones. Glucocorticoids entrain and synchronize core clocks in peripheral tissues and entrain glucocorticoid responsive genes. Peripheral clocks drive rhythmic expression of clock‐controlled genes. Endocrine rhythms, glucocorticoid responsive genes, and clock‐controlled genes propagate rhythms across physiological systems.