Abstract
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.
| Original language | English |
|---|---|
| Article number | 106436 |
| Pages (from-to) | 1-6 |
| Number of pages | 6 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 236 |
| Early online date | 28 Nov 2023 |
| DOIs | |
| Publication status | Published - Feb 2024 |
Bibliographical note
Funding Information:This work has been supported by the National Research Foundation of South Africa (Grant Number SRUG2204052159 , to KHS); the Academy of Medical Sciences UK (Newton Advanced Fellowship NAF004\1002, to KHS); the Wellcome Trust (Investigator Grant WT209492/Z/17/Z , to WA); and a SARChI DST/NRF grant ( 82813 , to JS).
Publisher Copyright:
© 2023 The Authors
Funding
This work has been supported by the National Research Foundation of South Africa (Grant Number SRUG2204052159 , to KHS); the Academy of Medical Sciences UK (Newton Advanced Fellowship NAF004\1002, to KHS); the Wellcome Trust (Investigator Grant WT209492/Z/17/Z , to WA); and a SARChI DST/NRF grant ( 82813 , to JS).
Keywords
- 17β-hydroxysteroid dehydrogenase
- AKR1C3
- Androgen biosynthesis
- HSD11B1
- HSD17B3
- Intracrinology