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Cited by 25Hormonal and reproductive studiesAdrenal Hormones and DisordersSteroid Chemistry and Biochemistry

The A-ring reduction of 11-ketotestosterone is efficiently catalysed by AKR1D1 and SRD5A2 but not SRD5A1

Open access
Barnard, Lise, Nikolaou, Nikolaos, Louw, Carla, Schiffer, Lina, Gibson, Hylton, Gilligan, Lorna C., Gangitano, Elena, Snoep, Jacky +3 more·2020·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/j.jsbmb.2020.105724
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Abstract

Testosterone and its 5α-reduced form, 5α-dihydrotestosterone, were previously thought to represent the only active androgens in humans. However, recent studies have shown that the potent androgen, 11-ketotestosterone, derived from the adrenal androgen precursor, 11β-hydroxyandrostenedione, may in fact serve as the primary androgen in healthy women. Yet, despite recent renewed interest in these steroids, their downstream metabolism has remained undetermined. We therefore set out to investigate the metabolism of 11-ketotestosterone by characterising the 5α- or 5β-reduction commitment step. We show that inactivation of 11-ketotestosterone is predominantly driven by AKR1D1, which efficiently catalyses the 5β-reduction of 11-ketotestosterone, committing it to a metabolic pathway that terminates in 11-ketoetiocholanolone. We demonstrate that 5α-reduction of 11-ketotestosterone is catalysed by SRD5A2, but not SRD5A1, and terminates in 11-ketoandrosterone, but is only responsible for a minority of 11-ketotestosterone inactivation. However, as 11-ketoetiocholanolone is also generated by the metabolism of the glucocorticoid cortisone, 11-ketoandrosterone should be considered a more specific urinary marker of 11-ketotestosterone production.

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Crossref · 10.1016/j.jsbmb.2020.105724

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  • This information aids the diagnosis of hormonal overproduction syndromes, e.g. Cushing syndrome or tumors, as well as in assessing compliance with hormonal therapy in CAH.

    “This information aids the diagnosis of hormonal overproduction syndromes, e.g.Cushing syndrome or tumors, as well as in assessing compliance with hormonal therapy in CAH (298,299).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [299]

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Authors
Barnard, L., Nikolaou, N., Louw, C., Schiffer, L., Gibson, H., Gilligan, L. C., Gangitano, E., Snoep, J., Arlt, W., Tomlinson, J. W., & Storbeck, K.-H.
Affiliations
  • Stellenbosch University (ZA)
  • Churchill Hospital (GB)
  • University of Birmingham (GB)
  • University Hospitals Birmingham NHS Foundation Trust (GB)
Corresponding author
Storbeck, Karl-Heinz
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2020-09
Volume
202
Pages
105724
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/j.jsbmb.2020.105724
OpenAlex
W3039496015
Cited by
25
References
23
Citations by year
2026: 2 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 1 · 2021: 7
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
  • Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Academy of Medical Sciences
  • Wellcome Trust
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Keywords
11-ketotestosterone, steroid metabolism, AKR1D1, SRD5A2, SRD5A1, 5α-reduction, 11β-hydroxyandrostenedione, adrenal androgens, urinary biomarkers
MeSH terms
Catalysis, Cortisone, Female, Humans, Liver, Membrane Proteins, Oxidation-Reduction, Oxidoreductases, Testosterone, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Cell Line, Tumor

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