Rhythms of acth and corticosteroid secretion in health and disease, and their experimental modification

Abstract

Detailed (q 5–30 min) sampling studies of both plasma ACTH and cortisol concentrations in normal human subjects demonstrates an early morning major circadian rise and a decline over the subsequent 24 h period, on which are superimposed lesser, episodic fluctuations (both synchronous and asynchronous) of plasma ACTH and cortisol concentrations. Marked concordance of bioassayable and immunoassayable plasma ACTH concentrations is present. The results of studies of ACTH-cortisol periodicity in patients with localized CNS disease or ocular blindness support the thesis of a neural origin of such periodicity. It is suggested that such a periodicity is endogenous, with the observed time of peaking related to some aspect(s) of the sleep-wake cycle, but synchronized by the dark-light cycle. Animal studies indicate that altered feeding schedules (without alteration of light-dark cycles) can alter the phase of corticosteroid periodicity, perhaps by alteration of the sleep-wake cycle. The presence of abnormal pituitary-adrenal periodicity in patients with Cushing's disease in remission lends support to the thesis of a neural etiology of this disease. Alteration of neonatal corticosteroid levels in the rat is associated with only temporary disruption of the normal periodicity of plasma cortocosteroid levels, and alterations of neonatal CNS amine content is not associated with any disruption of such periodicity.