ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Nat Rev Endocrinol. 2020; 16(5): 284–296. PMID: 32203405.

The adrenal gland is the primary source of 11-oxygenated 19-carbon steroids, also termed 11-oxyandrogens, which have several roles in human physiology and disease. These include 11β-hydroxyandrostenedione (11OHA4), 11-Ketotestosterone, (downstream metabolite of 11OHA4, mostly produced in peripheral tissues), and its 5α-reduced product, 11-ketodihydrotestosterone (1). The 11-oxyandrogens are bioactive androgens, with potencies equivalent to those of testosterone and dihydrotestosterone, while concentrations of 11-oxyandrogens are elevated in several disorders of androgen excess (2).

This narrative review summarizes and discusses the physiology and pathology of adrenal C19 steroids, emphasizing the previously under-recognized roles of 11-oxyandrogens both as part of pathophysiological mechanisms as well as potential biomarkers, of disease control in conditions of androgen excess, such as Congenital Adrenal Hyperplasia (CAH). Of particular interest to Pediatric Endocrinologists is the potential of use as biomarkers of disease control in CAH because, in contrast to more extensively studied traditional androgens, circulating 11-oxyandrogens concentrations are highly adrenal specific and do not demonstrate variation due to age or steroid treatment (3, 4). Finally, the 11-oxyandrogens appear to be major contributors to the androgen excess of premature adrenarche (5).

References:

1. Miller, W. L. & Auchus, R. J. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr. Rev. 32, 81–151 (2011).

2. Storbeck, K. H. et al. 11β- Hydroxydihydrotestosterone and 11- ketodihydrotestosterone, novel C19 steroids with androgenic activity: a putative role in castration resistant prostate cancer? Mol. Cell. Endocrinol. 377, 135–146 (2013).

3. Turcu, A. F. et al. Adrenal- derived 11- oxygenated 19- carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency. Eur. J. Endocrinol. 174, 601–609 (2016).

4. Kamrath, C., Wettstaedt, L., Boettcher, C., Hartmann, M. F. & Wudy, S. A. Androgen excess is due to elevated 11-oxygenated androgens in treated children with congenital adrenal hyperplasia. J. Steroid Biochem. Mol. Biol. 178, 221–228 (2018).

5. Rege, J. et al. 11-Ketotestosterone is the dominant circulating bioactive androgen during normal and premature adrenarche. J. Clin. Endocrinol. Metab. 103, 4589–4598 (2018).