The glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 catalyzes the activation of testosterone.

Female Humans Testosterone Androstenedione 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics Glucocorticoids Molecular Docking Simulation Hydroxyprostaglandin Dehydrogenases 3-Hydroxysteroid Dehydrogenases 17-Hydroxysteroid Dehydrogenases / genetics
17β-hydroxysteroid dehydrogenase AKR1C3 Androgen biosynthesis HSD11B1 HSD17B3 Intracrinology

Journal

The Journal of steroid biochemistry and molecular biology
ISSN: 1879-1220
Titre abrégé: J Steroid Biochem Mol Biol
Pays: England
ID NLM: 9015483

Informations de publication

Date de publication:
02 2024
Historique:
received: 07 11 2023
revised: 23 11 2023
accepted: 26 11 2023
medline: 12 1 2024
pubmed: 1 12 2023
entrez: 30 11 2023
Statut: ppublish

Résumé

Testosterone biosynthesis from its precursor androstenedione is thought to be exclusively catalysed by the 17β-hydroxysteroid dehydrogenases-HSD17B3 in testes, and AKR1C3 in the ovary, adrenal and peripheral tissues. Here we show for the first time that the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) can also catalyse the 17β-reduction of androstenedione to testosterone, using a combination of in vitro enzyme kinetic assays, mathematical modelling, and molecular docking analysis. Furthermore, we show that co-expression of HSD11B1 and AKR1C3 increases testosterone production several-fold compared to the rate observed with AKR1C3 only, and that HSD11B1 is likely to contribute significantly to testosterone production in peripheral tissues.

Identifiants

DOI: 10.1016/j.jsbmb.2023.106436 PMID: 38035948
pubmed: 38035948
pii: S0960-0760(23)00192-9
doi: 10.1016/j.jsbmb.2023.106436
pii:
doi:

Substances chimiques

Testosterone 3XMK78S47O
Androstenedione 409J2J96VR
11-beta-Hydroxysteroid Dehydrogenase Type 1 EC 1.1.1.146
Glucocorticoids 0
Hydroxyprostaglandin Dehydrogenases EC 1.1.1.-
3-Hydroxysteroid Dehydrogenases EC 1.1.-
17-Hydroxysteroid Dehydrogenases EC 1.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106436

Subventions

Organisme : Medical Research Council
ID : MC_UP_1605/15
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auteurs

Imken Oestlund (I)

Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.

Jacky Snoep (J)

Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa; Molecular Cell Biology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Lina Schiffer (L)

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.

Martin Wabitsch (M)

Division of Pediatric Endocrinology and Diabetes, University Hospital of Ulm, Ulm, Germany.

Wiebke Arlt (W)

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College, London, UK; Medical Research Council Laboratory of Medical Sciences, London, UK.

Karl-Heinz Storbeck (KH)

Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. Electronic address: storbeck@sun.ac.za.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Hormones gonadiques › Hormones sexuelles stéroïdiennes › Congénères de la testostérone › Testostérone › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Hormones gonadiques › Hormones sexuelles stéroïdiennes › Congénères de la testostérone › Androstènedione › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › 11-beta-Hydroxysteroid dehydrogenases › 11-beta-Hydroxysteroid dehydrogenase type 1 › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Glucocorticoïdes › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de docking moléculaire › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › Hydroxyprostaglandine dehydrogenases › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › Hydroxysteroid dehydrogenases › 3-Hydroxysteroid dehydrogenases › The glucocorticoid-activating enzyme...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › Hydroxysteroid dehydrogenases › 17-Hydroxysteroid dehydrogenases › The glucocorticoid-activating enzyme...