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

Area of Science:

• Endocrinology
• Pediatric Endocrinology
• Steroid Biochemistry

Background:

• Adrenarche involves increased adrenal androgens like dehydroepiandrosterone sulfate (DHEA-S).
• Premature adrenarche (PremA) is linked to adverse metabolic outcomes.
• The specific bioactive androgens driving these changes are not fully understood.

Purpose of the Study:

• To characterize the adrenal androgen profile in girls with PremA.
• To identify key bioactive androgens contributing to adrenarche and PremA.

Main Methods:

• Mass spectrometry was used to measure 19 steroids, including testosterone (T) and its 11-oxygenated derivatives.
• Sera from girls with PremA and age-matched controls were analyzed.
• Androgen receptor activity was assessed.

Main Results:

• Levels of dehydroepiandrosterone, DHEA-S, androstenediol-3-sulfate, T, and 11-ketotestosterone (11KT) increased with adrenarche.
• Girls with PremA showed elevated T, 11β-hydroxytestosterone (11OHT), and 11KT compared to controls.
• 11KT concentrations exceeded those of T and 11OHT, and 11KT demonstrated potent androgenic activity.

Conclusions:

• 11-ketotestosterone (11KT) is the dominant bioactive androgen during childhood adrenarche and PremA.
• The potent androgenic capacity of 11KT suggests its role in the observed phenotypic changes.