J. Endocrinol. Invest. 10. 267, 1987 Control of circadian and episodic variations of adrenal androgens secretion in man C. Lejeune-Lenain*, E. Van Cauter**' ****, D. Desir***, M. Beyloos***, and J.R.M. Franckson* *Department of Medical Chemistry, **Institute of Interdisciplinary Research, ***Department of Endocrinology, Free University of Brussels, Brussels, Belgium, ****Department of Medicine, The University of Chicago, Chicago, Illinois, USA ABSTRACT. The 24-h profiles of plasma cortisol (F), 11-J3-hydroxyandrostenedione (11 OHAD), an- drostenedione (AD), dehydroisoandrosterone (DHEA) and testosterone (T) were obtained simulta- neously in 11 normal males sampled at 15-min intervals. The data were submitted to a detailed quantitative analysis including the estimation ofthe circadian rhythm and ofthe 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 oftotally 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 11 OHAD), 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 > 0.75; p< 0.001) was found between the 4 adrenal hormones in each individual; a looser but significant correlation (r>0.30; p<0.001) was also detected between T and its partial precursors (AD and DHEA) and between T and the purely adrenal hormones: F and 11 OHAD (r > 0.30; P < 0.01). The pulsatility of the corticotrophic axis was readily transmitted to the secretory pattern of 11 OHAD, 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: (1) 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; (2) demonstrate the existence of a partial synchronization of adrenal and testicular pulsatile variations; (3) suggest that, throughout the afternoon, a common mechanism may influence the slow variations of adrenal hormones and of testicular testosterone. INTRODUCTION Circadian and episodic variations of plasma cortisol (F) levels in normal subjects are well documented (1). In contrast, relatively little quantitative data are available concerning the temporal fluctuations of the adrenal androgens 11-f3-hydroxyandrostenedione (11 OHAD), dehydroepiandrosterone (DHEA) and androstenedi- one (AD). The existence of a circadian rhythm has been demon- strated for each of them. Its dependence upon the Key-words. Cortisol, adrenal androgens, testosterone, circadian rhythm, episodiC pulses, cpncomltanc8, synchronization Correspondence C Leleune-Lenaln, Chlmie Medlcale, Hopital Unlversltalre Saint Pierre, Rue Haute 322, B-1 000 Bruxelles, Belgium Received April 21, 1986; accepted March 6, 1987 267 fluctuations of pituitary ACTH was assumed on the basis of a visual comparison of the 24-h profile with that of cortisol (2-9). However, such an examination did not allow the detection of possible gonadal inputs in the profiles of DHEA and AD, steroids of both gonadal and adrenal origin in adult man, The aim of the present study was to obtain a quantita- tive analysis of the circadian and episodic variations of plasma 11 OHAD, DHEA and AD levels and to compare them with those of F and 1. These comparisons could possibly disclose either a complete synchronization of adrenal secretion or spe- cific interrelationships between some of these hor- mones. Such interrelationships could result either from a common function particularly sensitive to ACTH, such as 11-hydroxylation for F and 11 OHAD (10) or from a precursor-derivative link, such as the one relat-