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Substrate multispecificity among 20β-hydroxysteroid dehydrogenase type 2 members
Janina Tokarz1, Jutta Lintelmann1, Gabriele Möller1
1Helmholtz Zentrum München, German Research Center for Environmental Health, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany.
Molecular and Cellular Endocrinology
|April 22, 2020
Summary
Hydroxysteroid dehydrogenases (HSDs) are key steroid regulators. This study reveals 20β-HSD type 2 enzymes metabolize diverse glucocorticoids, suggesting varied species-specific functions.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Steroids are crucial for numerous physiological functions.
- Hydroxysteroid dehydrogenases (HSDs) regulate steroid levels through pre- and post-receptor metabolism.
- The 20β-HSD type 2 subfamily includes six members across six species, with the zebrafish ortholog known for cortisone conversion and cortisol catabolism.
Purpose of the Study:
- To determine the substrate specificities of all known 20β-HSD type 2 enzymes.
- To investigate their roles in steroid metabolism, particularly within the glucocorticoid biosynthesis pathway.
Main Methods:
- Development and validation of a liquid chromatography-mass spectrometry (LC-MS) method for quantifying steroid substrates and products.
- Enzyme activity assays using recombinantly expressed 20β-HSD type 2 enzymes.
Main Results:
- The LC-MS method accurately quantified steroid substrates and their 20β-reduced products.
- All investigated 20β-HSD type 2 enzymes demonstrated the ability to catalyze the 20β-reduction of various glucocorticoid biosynthesis steroids.
- Significant multispecificity was observed among these homologous enzymes.
Conclusions:
- 20β-HSD type 2 enzymes are multispecific, reducing a wide range of glucocorticoid pathway steroids.
- This broad substrate preference suggests diverse and species-specific physiological roles for these enzymes in different organisms.
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