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

The circadian rhythm of glucocorticoids has long been recognised within the last 75 years. Since the beginning, researchers have sought to identify basic mechanisms underlying the origin and emergence of the corticosteroid circadian rhythmicity among mammals. Accordingly, Young, Hall and Rosbash, laureates of the 2017 Nobel Prize in Physiology or Medicine, as well as Takahashi's group among others, have characterised the molecular cogwheels of the circadian system, describing interlocking transcription/translation feedback loops essential for normal circadian rhythms. Plasma glucocorticoid circadian variation depends on the expression of intrinsic clock genes within the anatomic components of the hypothalamic-pituitary-adrenal axis, which are organised in a hierarchical manner. This review presents a general overview of the glucocorticoid circadian clock mechanisms, highlighting the ontogeny of the pituitary-adrenal axis diurnal rhythmicity as well as the involvement of circadian rhythm abnormalities in the physiopathology and diagnosis of Cushing's disease.