Interactions of the circadian CLOCK system and the HPA axis.
Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with one another at different signaling levels and dysregulation of either system can lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications.
Nader
Nancy
N
Unit on Molecular Hormone Action, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Chrousos
George P
GP
Kino
Tomoshige
T
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D003480:Cushing Syndrome / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology
D001786:Blood Glucose; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid