Circadian Rhythms of 11-oxygenated C19 Steroids and ∆5-Steroid Sulfates in Healthy Men.

Abstract

BACKGROUND\nMany hormones display distinct circadian rhythms, driven by central regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) are elevated in congenital adrenal hyperplasia and other disorders, but their circadian patterns have not been characterized.\n\n\nPARTICIPANTS AND METHODS\nPeripheral blood was collected every 2 h over 24 h from healthy volunteer men (10 young, 18-30 years, and 10 older, 60-80 years). We used mass 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 ∆5-steroid sulfates. Diurnal models including: mesor (rhythm adjusted median), peak, and nadir concentrations, acrophase, and amplitude were computed.\n\n\nRESULTS\n11OHA4 followed a rhythm similar to cortisol: acrophase, 8AM, nadir, 9PM and were similar in young and old men. 11KT had similar diurnal patterns, but the peak was lower in older than in young men, as was the case for A4. All 4 steroid sulfates were higher in young vs. older men. PregS and 17-hydroxypregnenolone sulfate (17OHPregS) showed sustained elevations between 8AM-6PM, and nadirs around midnight, while DHEAS and AdiolS displayed minimal diurnal variations. All 4 11-oxyandrogens correlated 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 adrenal origin and ACTH governance.\n\n\nCONCLUSIONS\n11-oxyandrogens, PregS, and 17OHPregS display distinct circadian and age variations, which should be accounted for when used as clinical biomarkers.