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Circadian rhythms of 11-oxygenated C19 steroids and Δ5-steroid sulfates in healthy men

Abstract:

Background: Many hormones display distinct circadian rhythms, driven by ce ntral regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) ar e elevated in congenital adrenal hyperplasia and other disorders, but their c ircadian patterns have not been characterized. Participants and methods: Peripheral blood was collected every 2 h over 24 h from health y volunteer men (10 young, 18-30 years, and 10 older, 60-80 years). We used mas s spectrometry to quantify 15 steroids, including androstenedione (A4), testosterone (T), 11β-hydroxy- and 11-ketotestosterone (11OHT, 11KT),11β-hydroxy- and 11-ketoandrostenedione (11OHA4, 11KA4), and 4 Δ5-steroid sulfates. Diurnal models including mesor (rhythm adjus ted median), peak, and nadir concentrations, acrophase, and amplitu de were computed. Results: 11OHA4 followed a rhythm similar to cortisol: Acrophase 8:00 h , nadir 21:00 h and were similar in young and old men. 11KT had similar diurnal patterns, but the peak was lo wer in older than in young men, as was the case for A4. All four steroid sulfates were higher in young vs older men. Pr egS and 17-hydroxypregnenolone sulfate (17OHPregS) showed sustained elevations between 8:00 and 18:00 h, and nadir s around midnight, while DHEAS and AdiolS displayed minimal diurnal variations. All 4 11-oxyandrogens cor related tightly with cortisol (r from 0.54 for 11OHT to 0.81 for 11OHA4, P < 0.0001 for all), but very weakly with T, supporting their adre nal origin and ACTH governance. Conclusions: 11-Oxyandrogens, PregS, and 17OHPregS display distinct circadi an and age variations, which should be accounted for when used as clinical biomarkers.