Circadian clock control of endocrine factors

Adequate circadian oscillation of endocrine factors is essential in the maintenance of metabolic homeostasis. The authors of this Review explain the influence of extrinsic and intrinsic factors on endocrine circadian rhythms and how dysregulation of these rhythms can lead to disease in animals and humans. They also discuss therapeutic strategies to restore circadian rhythmicity and improve metabolism. Organisms experience dramatic fluctuations in demands and stresses over the course of the day. In order to maintain biological processes within physiological boundaries, mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors have an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 h period, but so too does responsiveness of target tissues to these signals or stimuli. Emerging evidence suggests that these daily endocrine oscillations do not occur solely in response to behavioural fluctuations associated with sleep–wake and feeding–fasting cycles, but are orchestrated by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks by genetic and/or environmental factors seems to precipitate numerous common disorders, including the metabolic syndrome and cancer. Collectively, these observations suggest that strategies designed to realign normal circadian rhythmicities hold potential for the treatment of various endocrine-related disorders.