Discovery of a novel enzyme mediating glucocorticoid catabolism in fish: 20beta-hydroxysteroid dehydrogenase type 2
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Hydroxysteroid dehydrogenases (HSDs) are involved in metabolism and pre-receptor regulation of steroid hormones. While 17beta-HSDs and 11beta-HSDs are extensively studied in mammals, only few orthologs are characterized in fish. We discovered a novel zebrafish HSD candidate closely related to 17beta-HSD types 3 and 12, which has orthologs in other species. The enzyme catalyzes the conversion of cortisone to 20beta-hydroxycortisone identified by LC-MS/MS. We named the new enzyme 20beta-HSD type 2. All 20beta-HSD type 2 orthologs localize in the endoplasmic reticulum. Zebrafish 20beta-HSD type 2 is expressed during embryonic development showing the same expression pattern as 11beta-HSD type 2 known to oxidize cortisol to cortisone. In adult tissues 20beta-HSD type 2 shows a ubiquitous expression pattern with some minor sex-specific differences. In contrast to other enzymes metabolizing C21-steroids and being mostly involved in reproduction we propose that novel type 2 20beta-HSDs in teleost fish are important enzymes in cortisol catabolism.
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The human enzyme(s) responsible for formation of the 20β-hydroxy isomers of the cortols and cortolones has not yet been identified.
“the human enzyme(s) responsible for the formation of the 20β-hydroxy isomers of the cortols and cortolones has not yet been identified.”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [254]
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井尻, 成. (2019) · Comparative Endocrinology · doi:10.5983/nl2008jsce.45.121
Penghui, H. U. O., Chen, S., Huang, J., Yang, Y., Bai, Z., Xie, Y., & Lai, X. (2025) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2025.106929
Yatung, S., Ralte, L., & Trivedi, A. K. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.107041
Streltsova, Y., Reinwald, H., Ayobahan, S. U., Hollert, H., Teigeler, M., Eilebrecht, E., Pamminger, T., & Eilebrecht, S. (2026) · Aquatic Toxicology · doi:10.1016/j.aquatox.2026.107995
- Authors
- Tokarz, J., Mindnich, R., Norton, W., Möller, G., Hrabé de Angelis, M., & Adamski, J.
- Affiliations
- Helmholtz Munich (DE)
- University of Pennsylvania (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Adamski, Jerzy
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 349
- Issue
- 2
- Pages
- 202-213
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2019185881
- Cited by
- 48
- References
- 60
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 2 · 2016: 5 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- mediatum.ub.tum.de
- Licence
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Deutsche Forschungsgemeinschaft (AD 127/10-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- cortisone, zebrafish, hydroxysteroid dehydrogenase, steroid metabolism, endoplasmic reticulum localization, embryonic development, sex-specific gene expression, teleosts
- MeSH terms
- Amino Acid Sequence, Animals, Cloning, Molecular, Cortisone, Cortisone Reductase, Endoplasmic Reticulum, Female, HeLa Cells, Humans, Hydrocortisone, Isoenzymes, Molecular Sequence Data, Phylogeny, Transfection, Zebrafish, Sequence Homology, Amino Acid, Gene Expression Regulation, Developmental, Fish Proteins, Genetic Association Studies, HEK293 Cells
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