Ole-Martin Fuskevåg ab, Torkild Pettersen b and Guri Grimnes b,c
a Department of Laboratory Medicine, University Hospital of North Norway
b Department of Clinical Medicine, UiT, The Arctic University of Norway
c Division of Medicine, University Hospital of North Norway, Tromsø, Norway
Email: Ole.Fuskevag@unn.no
The presence of 11-oxygenated androgens (11-OxyA) have been recognized in humans for decades, but their role remains poorly understood. These potent and primarily adrenal-derived androgens have gained increasing attention due to their elevated levels in various hyperandrogenic disorders. 11β-hydroxyandrostenedione (11OHA4) has been established to be a precursor for the 11β-hydroxytestosterone (11OHT), 11-ketoandrostenedione (11KA4) and notably 11-ketotestosterone (11KT). 11KT has been studied for decades in bony (teleost) fishes, such as salmon, where it serves as the principal androgen driving sexual maturation. 11-OxyA play a significant role together with testosterone and dihydrotestosterone particularly in women and children. Androgen excess disorders are common, affecting up to 15% of women. 11-OxyA show promise as biomarkers for endocrine disorders. Because they originate specifically from the adrenal gland, these androgens may help distinguish adrenal from ovarian sources of hyperandrogenism. Elevated levels of 11-OxyA have been reported in the following conditions: Polycystic Ovary Syndrome (PCOS), Congenital Adrenal Hyperplasia (CAH), Premature Adrenarche, Severe Insulin Resistance (SIR), Cushing’s Disease, and in association with type 2 diabetes mellitus development.
Several research projects focus on quantifying 11-OxyA and other steroid hormones in human and fish serum. A LC-MS/MS method was therefore developed owing to its high sensitivity and specificity. Steroid hormones are extracted from serum by liquid–liquid extraction performed on a liquid-handling robot in 96-well plates to remove proteins and other interfering compounds. To ensure accurate and reliable sample results, we employ donor samples, quality controls, and isotopically labeled internal standards together with the calibrators. Chromatographic separation of steroid hormones is achieved on a Waters Acquity Cortecs T3 column (120 Å, 1.6 μm, 2.1 × 100 mm), and MRM data are acquired in both positive and negative ESI modes.
References
Turcu, A.F., Rege, J., Auchus, R.J. et al. 11-Oxygenated androgens in health and disease. Nat Rev Endocrinol 16, 284–296 (2020). https://doi.org/10.1038/s41574-020-0336-x.
Skjold, V., Rørvik, KA., Sveen, L., Burgerhout, E., Mota, VC., Weihe, R. et al. Gradually decreasing daylength after smoltification induced by “winter signal“reduced sexual maturation in male Atlantic salmon. Front Aquac 2, 1-20 (2024). https://doi.org/10.3389/faquc.2023.1235584.
Allaoui, G., Rylander C., Fuskevåg OM., et al. Longitudinal assessment of classic and 11-oxygenated androgen concentrations and their association with type 2 diabetes mellitus development: the Tromsø study. Acta Diabetol. 61(7), 847-857 (2024). https://doi:10.1007/s00592-024-02266-5.
Pettersen, T., Fuskevåg, OM., Figenschau, YA., Evensen, EK., Furberg, AS., Winther, A., Grimnes, G. 11-oxygenated androgens in healthy young adults. Does use of hormonal contraceptives matter? The Fit Futures Study. J Endocrinol Invest, under review.