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11-ketotestosterone is the dominant circulating bioactive androgen during normal and premature adrenarche
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Context: Adrenarche refers to the rise of dehydroepiandrosterone sulfate (DHEA-S) associated with the development of a functional adrenal zona reticularis. Clinical features of adrenarche include onset of body odor, axillary hair, and pubic hair, which reflect increased androgen action. An early rise in adrenal androgens, or premature adrenarche (PremA), is a risk factor for adverse metabolic profiles in adolescence and adulthood. The bioactive androgens associated with adrenarche and PremA remain poorly understood. The adrenal gland is a potential source of testosterone (T) and the 11-oxygenated derivatives 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT). Objective: The objective of this study was to characterize the adrenal androgen biome contributing to adrenarche and PremA. Participants and Methods: With the use of mass spectrometry, 19 steroids including the 11-oxygenated derivatives of T were measured in sera obtained from girls with PremA (n = 37; 4 to 7 years) and age-matched girls (n = 83; 4 to 10 years). Results: In reference population girls, dehydroepiandrosterone, DHEA-S, androstenediol-3-sulfate, T, and 11KT all increased at the onset of adrenarche (6 to 8 years) and beyond (9 to 10 years) (P < 0.05 vs younger subjects 4 to 5 years). T, 11OHT, and 11KT were further elevated in PremA vs age-matched girls (P < 0.001). Circulating concentrations of 11KT during adrenarche and PremA exceeded those of T and 11OHT (11KT > T ≥ 11OHT). Androgen receptor activity and nuclear translocation studies demonstrated that 11KT is a potent androgen similar to T. Conclusions: Our findings suggest that 11KT is the dominant bioactive androgen in children during adrenarche and PremA. Its androgenic capacity suggests that it may be responsible for the phenotypic changes seen in these phenomena.
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“11KT is a potent androgen, with bioactivity similar to that of T (25–27).”
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 [25]
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“Although quantitatively abundant, DHEA and DHEAS have virtually no androgenic activity (25).”
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 [25]
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Metadata
- Authors
- 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.
- Affiliations
- University of Michigan (US)
- Department of Pediatrics, University of Michigan, Ann Arbor, MI
- Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
- Rocky Mountain Diabetes and Osteoporosis Center (US)
- The University of Texas Southwestern Medical Center (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-08-17
- Volume
- 103
- Issue
- 12
- Pages
- 4589-4598
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC6226603
- OpenAlex
- W2887296926
- Cited by
- 154
- References
- 75
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 23 · 2023: 20 · 2022: 19 · 2021: 31 · 2020: 22 · 2019: 10 · 2018: 2
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan (48109, 1K08DK109116)
- National Institutes of Health (UL1TR000433, UL1TR002240)
- College of Pharmacy, University of Michigan
- National Institute of General Medical Sciences (R01GM086596)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK109116, R01DK069950, R01DK043140)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- 11-ketotestosterone, premature adrenarche, adrenarche, adrenal androgens, 11β-hydroxytestosterone, testosterone, circulating androgens, androgen receptor activity, adrenal zona reticularis, children, DHEA sulfate
- MeSH terms
- Androgens, Child, Child, Preschool, Female, Humans, Puberty, Precocious, Mass Spectrometry, Testosterone, Cohort Studies, Zona Reticularis, Dehydroepiandrosterone Sulfate, Adrenarche
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