Once-a-Day Neurally Stimulated and Basal ACTH Secretion Phases in Man and Their Response to Corticoid Inhibition

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Abstract
The sensitivity of the ACTHsecreting system to corticoid inhibition was studied in normal subjects by measuring variations in excretion of urinary 17-OHCS induced by intravenous infusion of corticoids in different periods of the day (4–8 am; 4 am–4 pm; 8 am–4 pm; 4–8 pm; 8 pm–midnight; midnight–4 am). Submaximal infusion doses (660 μg/hr 6-methylprednisolone; 30 μg/hr dexamethasone) led to partial inhibition only in the nocturnal early morning hours and no inhibition in the period from 8 am to midnight; only massive doses of dexamethasone (200 μg/hr) produced inhibition in this latter period. The following hypothesis is put forward: The ACTH-secreting system has 2 daily activity phases with different control mechanisms. One in the nocturnal early morning hours is the result of neural activity directed to the hypothalamus, superimposed on the basal activity and responsible for the circadian rhythm. This once-a-day impulse would appear to be linked to the rapid eye movement sleep stages. Corticoid-induced inhibition in submaximal doses is possible only during this phase. The second phase is characterized by a steady basal activity lasting 24 hr. It is independent of the early morning hour impulse and is resistant to all but massive doses of corticoids.