Control of circadian and episodic variations of adrenal androgens secretion in man.

The 24-h profiles of plasma cortisol (F), 11-beta-hydroxyandrostenedione (11OHAD), androstenedione (AD), dehydroisoandrosterone (DHEA) and testosterone (T) were obtained simultaneously in 11 normal males sampled at 15-min intervals. The data were submitted to a detailed quantitative analysis including the estimation of the circadian rhythm and of the episodic variations as well as the evaluation of the concomitance of episodic pulses of different hormones. A bimodal circadian rhythm was detected in the various individual profiles. The major acrophase occurred in the morning earlier for T (around 04:00 h) than for the hormones of totally or partially adrenal origin (around 07:00 h); the secondary acrophase (around 17:00 h) and the main midnight nadir were common to all hormones. The amplitude of the rhythm was highest for purely adrenal hormones (F and 11OHAD), averaging 79 and 75%, respectively, lower for hormones of mixed origin (DHEA and AD), averaging 44 and 42%, respectively, and minimal for T (22%). The possible relationship between the circadian and pulsatile variations of the various steroids was estimated in each individual by calculating Pearson's standard coefficient of variation on all pairs of hormonal profiles. A very tight relationship (r greater than 0.75; p less than 0.001) was found between the 4 adrenal hormones in each individual; a looser but significant correlation (r greater than 0.30; p less than 0.001) was also detected between T and its partial precursors (AD and DHEA) and between T and the purely adrenal hormones: F and 11OHAD (r greater than 0.30; p less than 0.01). The pulsatility of the corticotrophic axis was readily transmitted to the secretory pattern of 11OHAD, DHEA and AD. Ninety-six percent of the F pulses were reflected in at least one other hormonal profile. Finally, we showed that concomitant pulses common to the five adrenal and gonadal patterns were more frequent than would be expected on the basis of chance. These results: demonstrate a total parallelism between the long-lasting secretory events and the episodic bursts of the 4 adrenal hormones showing that the reticular and fascicular zones of the adrenal respond to pituitary control as an homogeneous structure; demonstrate the existence of a partial synchronization of adrenal and testicular pulsatile variations; suggest that, throughout the afternoon, a common mechanism may influence the slow variations of adrenal hormones and of testicular testosterone.

Prolonged pulsatile administration of ovine corticotropin-releasing hormone in normal man.

The 24-h profiles of plasma ACTH and cortisol were determined at 15-min intervals in five normal men basally and during iv bolus injections of 25 micrograms ovine corticotropin-releasing hormone (oCRH) every 4 h for 72 h. Each oCRH injection was followed by a distinct elevation of plasma ACTH and cortisol levels, with a return to basal values before the next injection. The characteristics of the ACTH and cortisol pulses induced by 25 micrograms oCRH (i.e. 0.3-0.4 micrograms/kg) were similar to those observed in other studies with 1 microgram/kg human CRH. There was no significant blunting of oCRH-induced hormonal increments in the course of the 72-h study. On each oCRH injection day, the mean 24-h cortisol level was higher than that in the basal study, but there was no increase in the mean 24-h ACTH level. During the 72-h oCRH study, the preinjection ACTH and cortisol levels exhibited a diurnal variation, indicating persistence of the circadian periodicity of pituitary-adrenal activity. There was a diurnal variation of oCRH-induced ACTH increments, with highest responses at 0700 h. A small but not significant reverse trend was apparent for cortisol increments. Spontaneous pulses of ACTH and cortisol occurred throughout the 3 days of oCRH injections, and the total number of spontaneous and oCRH-induced pulses was similar to the number of spontaneous pulses observed in the basal study. All oCRH-induced and more than 90% of spontaneous cortisol pulses occurred concomitantly with an ACTH pulse. The variability of pulse increments was greater for ACTH than for cortisol. In conclusion, prolonged pulsatile administration of oCRH did not induce pituitary desensitization and did not suppress the endogenous circadian and pulsatile ACTH and cortisol variations.

Immediate and delayed alterations of adrenocorticotropin and cortisol nyctohemeral profiles after corticotropin-releasing factor in normal man.

Intravenous injections of 50 micrograms corticotropin-releasing factor (CRF) to four normal men at 0900 and 2300 h were followed by significant plasma ACTH and cortisol elevations, without changes in GH and PRL concentrations. The responses were more easily assessed late in the evening than in the morning, when they were superimposed upon the spontaneous hormonal variations. The initial hormonal response was always followed by a period of decreased hormonal values compared to control patterns. The normal pituitary-adrenal response to CRF was blunted or abolished by prior administration of dexamethasone. These data suggest that exogenous administration or CRF-induced endogenous production of glucocorticoids modulates the sensitivity of corticotropic cells to the action of CRF. Since normal ACTH and cortisol secretory episodes are likely to obscure the effects of CRF, stimulation tests for clinical purposes should be performed during the quiescent period, i.e. late in the evening.