Circadian Rhythms of 11-Oxygenated C19 Steroids and 5-Steroid Sulfates in Healthy Men
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In healthy individuals, 11-oxyandrogens display morning peaks and nocturnal nadirs, similar to cortisol.
“In healthy individuals, 11-oxyandrogens display morning peaks and nocturnal nadirs, similar to cortisol (22).”
From 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency (2021) · cites this paper as [22]
The Results report that 11OHA4 closely resembled cortisol, peaking around 8:00 h and reaching a nadir around 21:00 h; the Discussion describes similar circadian patterns for the other 11-oxyandrogens. The study sampled healthy men only, so it does not establish the pattern for healthy individuals generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPhysiologic cortisol synthesis has a characteristic circadian pattern, with an early morning peak and a late-night nadir.
“Physiologic cortisol synthesis has a characteristic circadian pattern, with an early morning peak and a late-night nadir (20–22).”
From 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency (2021) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Bases for Circadian Clocks
Dunlap, J. C. (1999) · Cell · doi:10.1016/s0092-8674(00)80566-8 · Cited by 2,900 · see citing works
Dissecting human adrenal androgen production
Rainey, W. E., Carr, B. R., Sasano, H., Suzuki, T., & Mason, J. I. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(02)00609-4 · Cited by 270 · see citing works
Self-citation11-Oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome
O’Reilly, M. W., Kempegowda, P., Jenkinson, C., Taylor, A. E., Quanson, J. L., Storbeck, K.-H., & Arlt, W. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3285 · Cited by 267 · see citing works
Review: Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy
Chan, S., & Debono, M. (2010) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018810380214 · Cited by 243 · see citing works
Turcu, A. F., Nanba, A. T., Chomic, R., Upadhyay, S. K., Giordano, T. J., Shields, J. J., Merke, D. P., Rainey, W. E., & Auchus, R. J. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-1181 · Cited by 231 · see citing works
Self-citationRege, J., Nakamura, Y., Satoh, F., Morimoto, R., Kennedy, M. R., Layman, L. C., Honma, S., Sasano, H., & Rainey, W. E. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2912 · Cited by 227 · see citing works
Self-citation11-Oxygenated androgens in health and disease
Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0336-x · Cited by 217 · see citing works
Self-citationLIU, C. H., LAUGHLIN, G. A., FISCHER, U. G., & YEN, S. S. C. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-4-900 · Cited by 155 · see citing works
Rege, J., Turcu, A., Kasa-Vubu, J. Z., Lerario, A. M., Auchus, G. C., Auchus, R. J., Smith, J. M., White, P. C., & Rainey, W. E. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00736 · Cited by 154 · see citing works
Self-citationPretorius, E., Africander, D. J., Vlok, M., Perkins, M. S., Quanson, J., & Storbeck, K.-H. (2016) · PLOS ONE · doi:10.1371/journal.pone.0159867 · Cited by 148 · see citing works
Reinberg, A., Lagoguey, M., Cesselin, F., Touitou, Y., Legrand, J.-C., Delassalle, A., Antreassian, J., & Lagoguey, A. (1978) · Acta Endocrinologica · doi:10.1530/acta.0.0880417 · Cited by 126 · see citing works
Adrenal Androgens and Androgen Precursors-Definition, Synthesis, Regulation and Physiologic Actions
Turcu, A., Smith, J. M., Auchus, R., & Rainey, W. E. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140006 · Cited by 113 · see citing works
Self-citation11-oxygenated C19 steroids Do not decline with age in women
Nanba, A. T., Rege, J., Ren, J., Auchus, R. J., Rainey, W. E., & Turcu, A. F. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-02527 · Cited by 113 · see citing works
Self-citationTurcu, A. F., Mallappa, A., Elman, M. S., Avila, N. A., Marko, J., Rao, H., Tsodikov, A., Auchus, R. J., & Merke, D. P. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3989 · Cited by 107 · see citing works
Self-citationThe effects of ACTH on steroid metabolomic profiles in human adrenal cells
Xing, Y., Edwards, M. A., Ahlem, C., Kennedy, M., Cohen, A., Gomez-Sanchez, C. E., & Rainey, W. E. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0493 · Cited by 101 · see citing works
Self-citationMerza, Z., Rostami‐Hodjegan, A., Memmott, A., Doane, A., Ibbotson, V., Newell‐Price, J., Tucker, G. T., & Ross, R. J. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02544.x · Cited by 98 · see citing works
11-Ketotestosterone Is a Major Androgen Produced in Human Gonads
Imamichi, Y., Yuhki, K., Orisaka, M., Kitano, T., Mukai, K., Ushikubi, F., Taniguchi, T., Umezawa, A., Miyamoto, K., & Yazawa, T. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2311 · Cited by 96 · see citing works
Dennedy, M. C., Annamalai, A. K., Smith, O. P., Freeman, N., Vengopal, K., Graggaber, J., Koulouri, O., Powlson, A., Shaw, A., Halsall, D. J., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2718 · Cited by 83 · see citing works
Abraham, G. E., Buster, J. E., KYLE, F. W., Corrales, P. C., & Teller, R. C. (1973) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-37-1-140 · Cited by 81 · see citing works
Comprehensive Analysis of Steroid Biomarkers for Guiding Primary Aldosteronism Subtyping
Turcu, A. F., Wannachalee, T., Tsodikov, A. D., Nanba, A. T., Ren, J., Shields, J. J., O’Day, P., Giacherio, D. A., Rainey, W. E., & Auchus, R. J. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13866 · Cited by 78 · see citing works
Self-citationSex differences in 11-oxygenated androgen patterns across adulthood
Davio, A., Woolcock, H., Nanba, A. T., Rege, J., O’Day, P., Ren, J., Zhao, L., Ebina, H., Auchus, R., Rainey, W. E., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa343 · Cited by 76 · see citing works
Self-citationDevelopment of a Novel Cell Based Androgen Screening Model
Campana, C., Rege, J., Turcu, A. F., Pezzi, V., Gomez-Sanchez, C. E., Robins, D. M., & Rainey, W. E. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.11.005 · Cited by 73 · see citing works
Self-citationVeldhuis, J., Yang, R., Roelfsema, F., & Takahashi, P. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3611 · Cited by 65 · see citing works
Self-citationGuignard, M., Pesquiès, P., Serrurier, B., Gomez-Mérino, D., & Reinberg, A. (1980) · European Journal of Endocrinology · doi:10.1530/acta.0.0940536 · Cited by 58 · see citing works
DHEAS for the prediction of subclinical Cushing’s syndrome: perplexing or advantageous?
Yener, S., Yilmaz, H., Demir, T., Seçil, M., & Çömlekçi, A. (2014) · Endocrine · doi:10.1007/s12020-014-0387-7 · Cited by 55 · see citing works
Fiet, J., Gourmel, B., Villette, J. M., Brérault, J.-L., Julien, R., Cathelineau, G., & DREUX, C. (2008) · Hormone Research · doi:10.1159/000179280 · Cited by 48 · see citing works
Gent, R., du Toit, T., Bloem, L. M., & Swart, A. C. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.02.013 · Cited by 41 · see citing works
Rezvani, I., Garibaldi, L. R., Digeorge, A. M., & Artman, H. G. (1983) · Pediatric Research · doi:10.1203/00006450-198302000-00010 · Cited by 33 · see citing works
Flagged first, then by citations
1 of the 29 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [14]Turcu AF, Zhao L, Chen X, Yang R, Rege J, Rainey WE, Veldhuis J & Auchus RJ. Supplemental data for: Circadian rhythms of 11-oxygenated C19 steroids and Δ5-steroid sulfates in healthy men [ zenodo.org], 2021. Deposited on 07/07/2021. (available from: 10.5281/zenodo.5077121) PMC8826489 34324429 · DOI
Cited by
Sorted by citations
The clinical and biochemical significance of 11-oxygenated androgens in human health and disease
Storbeck, K.-H., & O’Reilly, M. W. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad047 · Cited by 63 · see citing works
Schiffer, L., Kempegowda, P., Sitch, A. J., Adaway, J. E., Shaheen, F., Ebbehoj, A., Singh, S., McTaggart, M. P., O’Reilly, M. W., Prete, A., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvac017 · Cited by 42 · see citing works
Kelly, M. R., Yuen, F., Satterfield, B. C., Auchus, R. J., Gaddameedhi, S., Dongen, H. P. A. V., & Liu, P. Y. (2022) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac153 · Cited by 23 · see citing works
Self-citationBioactivity of 11 keto and hydroxy androgens in yeast and mammalian host cells
Handelsman, D. J., Cooper, E. R., & Heather, A. K. (2022) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2021.106049 · Cited by 22 · see citing works
Turcu, A. F., Mallappa, A., Nella, A. A., Chen, X., Zhao, L., Nanba, A. T., Byrd, J. B., Auchus, R. J., & Merke, D. P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.751191 · Cited by 20 · see citing works
“morning peaks and nocturnal nadirs, similar to cortisol (22).”
BackgroundSelf-citationBezuglov, E., Ahmetov, I. I., Lazarev, A. M., Mskhalaya, G. J., Talibov, O., Ustinov, V., Shoshorina, M., Bogachko, E., Azimi, V., Morgans, R., et al. (2023) · Physiology & Behavior · doi:10.1016/j.physbeh.2023.114344 · Cited by 22 · see citing works
Alterations in Pregnenolone and Testosterone Levels in Male Shift Workers
Bracci, M., Zingaretti, L., Martelli, M., Lazzarini, R., Salvio, G., Amati, M., Milinkovic, M., Ulissi, A., Medori, A., Vitale, E., et al. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20043195 · Cited by 16 · see citing works
Lee, C., O’Day, P., Stouffer, D. G., Auchus, R. J., & Turcu, A. F. (2025) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2025.106717 · Cited by 15 · see citing works
Self-citationReference intervals for serum 11-oxygenated androgens in children
Adriaansen, B. P. H., Oude-Alink, S., Swinkels, D. W., Schröder, M. A. M., Span, P. N., Sweep, F. C. G. J., der Grinten, H. L. C., & van Herwaarden, A. E. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae008 · Cited by 15 · see citing works
The role of 11-oxygenated androgens in prostate cancer
Snaterse, G., Hofland, J., & Lapauw, B. (2023) · Endocrine Oncology · doi:10.1530/eo-22-0072 · Cited by 5 · see citing works
The Landscape of Androgens in Cushing’s Syndrome
Nowotny, H. F., Braun, L., & Reisch, N. (2024) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2333-1907 · Cited by 5 · see citing works
Influence of ethanol consumption and food intake on serum concentrations of endogenous steroids
Thieme, D., Krumbholz, A., Bidlingmaier, M., Geffert, C., Hameder, A., Stöver, A., Graw, M., & Keiler, A. M. (2023) · Steroids · doi:10.1016/j.steroids.2023.109331 · Cited by 5 · see citing works
Chen, L., Chen, Y., Lin, F., Wang, J., Gao, H., & Liu, Y. (2025) · BMC Pulmonary Medicine · doi:10.1186/s12890-025-03519-x · Cited by 4 · see citing works
11-deoxycortisol positively correlates with T cell immune traits in physiological conditions
Peng, C., Jiang, X., Jaeger, M., van Houten, P., van Herwaarden, A. E., Koeken, V. A. C. M., Moorlag, S. J. C. F. M., Mourits, V. P., Lemmers, H., Dijkstra, H., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104935 · Cited by 5 · see citing works
Circadian variations in the elderly: A scoping review
Ferreira, L. L., Rosatto, N., Marzullo, P., & Bellan, M. (2024) · Chronobiology International · doi:10.1080/07420528.2024.2327456 · Cited by 1 · see citing works
Pettersen, T., Fuskevåg, O., Figenschau, Y., Evensen, E., Furberg, A., Winther, A., & Grimnes, G. (2026) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02793-0
Jin, X., Werner, H. M. J., & Romano, A. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.106958
The Circadian Rhythm of Male Reproductive Function
姜, 晓. (2026) · Nursing Science · doi:10.12677/ns.2026.156206
- Authors
- Turcu, A. F., Zhao, L., Chen, X., Yang, R., Rege, J., Rainey, W. E., Veldhuis, J. D., & Auchus, R. J.
- Affiliations
- University of Michigan (US)
- Mayo Clinic (US)
- Corresponding author
- Turcu, Adina F
- ORCID
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-10-01
- Volume
- 185
- Issue
- 4
- Pages
- K1-K6
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- PMC
- PMC8826489
- OpenAlex
- W3183336627
- Cited by
- 19
- References
- 29
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 2 · 2021: 2
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK109116, R01DK069950)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- circadian rhythm, C19 steroids, pregnenolone sulfate, steroid sulfates, androstenedione, testosterone, 11-ketotestosterone, age differences, cortisol, ACTH, healthy men
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Androgens, Blood Chemical Analysis, Circadian Rhythm, Humans, Hydroxysteroids, Ketosteroids, Male, Middle Aged, Mass Spectrometry, Sulfates, Young Adult, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
