Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa; Molecular Cell Biology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
J Steroid Biochem Mol Biol. 2024 Feb;236:106436. doi: 10.1016/j.jsbmb.2023.106436. Epub 2023 Nov 28.
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.
人们认为，从其前体雄烯二酮到睾丸酮的生物合成仅由 17β-羟甾类脱氢酶-HSD17B3 在睾丸中、由 AKR1C3 在卵巢、肾上腺和外周组织中催化。在这里，我们首次表明，糖皮质激素激活酶 11β-羟甾类脱氢酶类型 1（HSD11B1）也可以通过体外酶动力学测定、数学建模和分子对接分析，催化雄烯二酮的 17β-还原为睾丸酮。此外，我们表明，与仅 AKR1C3 观察到的速率相比，HSD11B1 与 AKR1C3 的共表达使睾丸酮的产生增加了几倍，并且 HSD11B1 很可能对外周组织中的睾丸酮产生有重要贡献。
