11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche

Juilee Rege, Adina F. Turcu, Josephine Z. Kasa-Vubu, Antonio M. Lerario, Gabriela C. Auchus, Richard J. Auchus, Joshua M. Smith, Perrin C White, William E. Rainey

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish (US)
Pages4589-4598
Number of pages10
JournalThe Journal of clinical endocrinology and metabolism
Volume103
Issue number12
DOIs
StatePublished - Dec 1 2018

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Adrenarche
Androgens
Hydroxytestosterones
Zona Reticularis
Dehydroepiandrosterone Sulfate
Derivatives
Hair
11-ketotestosterone
Androstenediol
Metabolome
Dehydroepiandrosterone
Androgen Receptors
Odors
Adrenal Glands
Sulfates
Mass spectrometry
Ecosystem
Testosterone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Rege, J., Turcu, A. F., Kasa-Vubu, J. Z., Lerario, A. M., Auchus, G. C., Auchus, R. J., ... Rainey, W. E. (2018). 11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche. The Journal of clinical endocrinology and metabolism, 103(12), 4589-4598. https://doi.org/10.1210/jc.2018-00736

11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche. / Rege, Juilee; Turcu, Adina F.; Kasa-Vubu, Josephine Z.; Lerario, Antonio M.; Auchus, Gabriela C.; Auchus, Richard J.; Smith, Joshua M.; White, Perrin C; Rainey, William E.

In: The Journal of clinical endocrinology and metabolism, Vol. 103, No. 12, 01.12.2018, p. 4589-4598.

Research output: Contribution to journalArticle

Rege, J, Turcu, AF, Kasa-Vubu, JZ, Lerario, AM, Auchus, GC, Auchus, RJ, Smith, JM, White, PC & Rainey, WE 2018, '11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche' The Journal of clinical endocrinology and metabolism, vol. 103, no. 12, pp. 4589-4598. https://doi.org/10.1210/jc.2018-00736
Rege, Juilee ; Turcu, Adina F. ; Kasa-Vubu, Josephine Z. ; Lerario, Antonio M. ; Auchus, Gabriela C. ; Auchus, Richard J. ; Smith, Joshua M. ; White, Perrin C ; Rainey, William E. / 11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche. In: The Journal of clinical endocrinology and metabolism. 2018 ; Vol. 103, No. 12. pp. 4589-4598.
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abstract = "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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AU - Turcu, Adina F.

AU - Kasa-Vubu, Josephine Z.

AU - Lerario, Antonio M.

AU - Auchus, Gabriela C.

AU - Auchus, Richard J.

AU - Smith, Joshua M.

AU - White, Perrin C

AU - Rainey, William E.

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N2 - 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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