Circadian rhythms of 11-oxygenated C19 steroids and ∆5-steroid sulfates in healthy men

in European Journal of Endocrinology
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  • 1 Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan, USA
  • | 2 School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
  • | 3 Endocrine Research Unit, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA
  • | 4 Department of Physiology and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA
  • | 5 Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA

Correspondence should be addressed to A F Turcu; Email: aturcu@umich.edu
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Background

Many 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.

Participants and methods

Peripheral 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.

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 lower in older than in young men, as was the case for A4. All four steroid sulfates were higher in young vs older men. PregS and 17-hydroxypregnenolone sulfate (17OHPregS) showed sustained elevations between 8:00 and 18:00 h, 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.

Conclusions

11-Oxyandrogens, PregS, and 17OHPregS display distinct circadian and age variations, which should be accounted for when used as clinical biomarkers.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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