Temporal Variation in Su-4885 Responsiveness in Man: Evidence in Support of Circadian Variation in ACTH Secretion

Publisher Website
Google Scholar
Abstract
To investigate the role of the pituitary-adrenal feedback mechanism in the regulation of the steroid circadian rhythm, a study was undertaken in the same group of normal subjects of the adrenocortical response to ACTH and Su-4885 (Metopirone) infused at different times in the 24 hr. The responses to ACTH as well as to Su-4885 demonstrated a circadian variation. The rise in 17-OHCS excretion induced by Su-4885 was greatest at the time of day when adrenocortical activity was maximal and least when adrenal secretory activity was minimal. Inhibition of 11β-hydroxylation was apparent from a fall in plasma cortisol concentration and the excretion of cortisol metabolites, irrespective of the time of drug administration. A modest decrease in adrenocortical responsiveness to ACTH at night has been confirmed but can hardly account for the marked temporal variation in the response to Su-4885. Since the adrenal response to Su-4885 is dependent upon the functional integrity of a central nervous system-pituitary ACTH mechanism, the present results are compatible with the suggestion that ACTH secretion occurs as a periodic event independent of the plasma cortisol concentration, but that the latter regulates the magnitude of the ACTH discharge. The data support the concept of a circadian variation in ACTH secretion, presumably the result of an inherent rhythmicity in the neural centers concerned with pituitary regulation.

This publication has 2 references indexed in Scilit: