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. 2017 Jun;24(3):252-259.
doi: 10.1097/MED.0000000000000334.

Clinical significance of 11-oxygenated androgens

Adina F Turcu  1 , Richard J Auchus
Affiliations

Clinical significance of 11-oxygenated androgens

Adina F Turcu et al. Curr Opin Endocrinol Diabetes Obes. 2017 Jun.

Abstract

Purpose of review: The adrenal gland is considered a source of weak androgens, such as dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. Emerging evidence proposes a set of 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as clinically important androgens. Such steroids include 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone. The present review will discuss the synthesis, androgenic activity, and clinical implications of the 11oxC19 steroids.

Recent findings: The clinical relevance of the 11oxC19 steroids resides in two key characteristics: the synthesis of all 11oxC19 originates predominantly in the adrenal cortex, and 11-ketotestosterone and its 5α-reduced metabolite, 11-ketodihydrotestosterone are potent agonists of the human androgen receptor, similar to the classic androgens testosterone and dihydrotestosterone, respectively. Recent studies have demonstrated higher than normal circulating levels of 11oxC19 steroids in patients with 21-hydroxylase deficiency and in polycystic ovary syndrome. The 11oxC19 steroids are also thought to contribute to castration-resistant prostate cancer progression. In addition, the 11oxC19 steroids might have clinical implications in adrenarche and postmenopausal women.

Summary: Future prospective studies are needed to establish the clinical utility of the 11oxC19 steroids for individualized patient care. Preliminary data suggest that these biomarkers hold promise to improve the evaluation and management of androgen excess disorders.

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Figures

Figure 1
Figure 1
Adrenal androgen synthesis. Preg, pregnenolone; 17OH-Preg, 17-hydroxypregnenolone; DHEA(S), dehydroepinadrosterone (sulfate); A-diol, androst-5-ene-3β,17β-diol; A4, androstenedione; T, testosterone; 11OHA4, 11β-hydroxyandrostenedione, 11KA4, 11-ketoandrostenedione; 11OHT, 11β-hydroxytestosterone; 11KT, 11-ketotestosterone; StAR, steroidogenic acute regulatory protein; CYP11A1, cholesterol side-chain cleavage; HSD3B2, 3β-hydroxysteroid dehydrogenase type 2; CYP17A1, 17α-hydroxylase/17,20-lyase; CYB5A, cytochrome b5 type A; CYP11B1, 11β-hydroxylase; AKR1C3, 17β-hydroxysteroid dehydrogenase type 5; HSD11B2, 11β-hydroxysteroid dehydrogenase, type 2; SULT2A1, sulfotransferase 2A1.
Figure 2
Figure 2
Adrenal steroidogenic pathways in 21-hydroxylase deficiency. DHEA, dehydroepinadrosterone; A4, androstenedione; T, testosterone; 11OHA4, 11β-hydroxyandrostenedione, 11KA4, 11-ketoandrostenedione; 11OHT, 11β-hydroxytestosterone; 11KT, 11-ketotestosterone; DHT, dihydrotestosterone; 11OHDHT, 11β-hydroxydihydrotestosterone; 11KDHT, 11-ketodihydrotestosterone; HSD3B2, 3β-hydroxysteroid dehydrogenase/isomerase type 2; CYP17A1, 17α-hydroxylase/17,20-lyase; CYB5A, cytochrome b5 type A; CYP11B1, 11β-hydroxylase; AKR1C3, 17β-hydroxysteroid dehydrogenase type 5; HSD11B2, 11β-hydroxysteroid dehydrogenase, type 2; SRD5A1/2, 5α-reductase, types 1 and 2; AKR1C2,4, aldo-keto reductase types 1C2 and 1C4; HSD17B6, 17β-hydroxysteroid dehydrogenase type 6.
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References

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