Glucocorticoid secretion: a circadian synchronizer of the human temporal structure

The circadian rhythm of glucocorticoid secretion represents an important endogenous synchronizer, a signal to place other bioperiodicities along an appropriate time scale. The results obtained both in experimental animals and in man by properly-timed administration of corticoids as well as personal observations in patients with Addison's disease given replacement therapy suggest that glucocorticoid action may not need continuous supply of hormone molecules to target cells but appropriate waves complying with the peripheral susceptibility. Furthermore, circadian changes in the susceptibility to glucocorticoid action may be phase-shifted among different targets. Evidence is presented that in human beings ACTH secretion is exquisitely sensitive to the negative feed-back effect by cortisol in the nocturnal hours following midnight, i.e. in a circadian stage preceding the acrophase of plasma glucocorticoid levels. In the circadian domain multiple rhythmic events, including chrono-feed-back and chrono-feed-forward mechanisms as well as the organization of steroid binding to plasma corticosteroid-binding globulin, provide stability, plasticity and economy to the activity of the entire hypothalamo-pituitary-adrenal system by conveying genetic and environmental control into a well-defined temporal program.