The DOI matches its Crossref record; 140 of the 146 references it cites were found in a registry or an index.
17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: Protein structures, functions, and recent progress in inhibitor development
Abstract
17β-Hydroxysteroid dehydrogenases (17β-HSDs) are oxidoreductases, which play a key role in estrogen and androgen steroid metabolism by catalyzing final steps of the steroid biosynthesis. Up to now, 14 different subtypes have been identified in mammals, which catalyze NAD(P)H or NAD(P)(+) dependent reductions/oxidations at the 17-position of the steroid. Depending on their reductive or oxidative activities, they modulate the intracellular concentration of inactive and active steroids. As the genomic mechanism of steroid action involves binding to a steroid nuclear receptor, 17β-HSDs act like pre-receptor molecular switches. 17β-HSDs are thus key enzymes implicated in the different functions of the reproductive tissues in both males and females. The crucial role of estrogens and androgens in the genesis and development of hormone dependent diseases is well recognized. Considering the pivotal role of 17β-HSDs in steroid hormone modulation and their substrate specificity, these proteins are promising therapeutic targets for diseases like breast cancer, endometriosis, osteoporosis, and prostate cancer. The selective inhibition of the concerned enzymes might provide an effective treatment and a good alternative to the existing endocrine therapies. Herein, we give an overview of functional and structural aspects for the different 17β-HSDs. We focus on steroidal and non-steroidal inhibitors recently published for each subtype and report on existing animal models for the different 17β-HSDs and the respective diseases. Article from the Special issue on Targeted Inhibitors.
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“Generally, these enzymes are multi-functional and often have overlapping substrate specificities and expression patterns, allowing for redundant enzymes to cover in case of deficiency of another enzyme [107,114].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [107]
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Metadata
- Authors
- Marchais-Oberwinkler, S., Henn, C., Möller, G., Klein, T., Negri, M., Oster, A., Spadaro, A., Werth, R., Wetzel, M., Xu, K., Frotscher, M., Hartmann, R. W., & Adamski, J.
- Affiliations
- Helmholtz Institute for Pharmaceutical Research Saarland (DE)
- Helmholtz Munich (DE)
- Saarland University (DE)
- Corresponding author
- Frotscher, Martin
- Hartmann, Rolf W.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 125
- Issue
- 1-2
- Pages
- 66-82
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2022118060
- Cited by
- 216
- References
- 146
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 16 · 2022: 5 · 2021: 16 · 2020: 16 · 2019: 12 · 2018: 19 · 2017: 11 · 2016: 13 · 2015: 19 · 2014: 15 · 2013: 14 · 2012: 11
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- 17β-hydroxysteroid dehydrogenase, enzyme inhibition, estrogen metabolism, androgen metabolism, steroidogenesis, nuclear steroid receptors, breast cancer, endometriosis, osteoporosis, prostate cancer, protein structure, animal models
- MeSH terms
- Amino Acid Sequence, Androgens, Animals, Breast Neoplasms, Enzyme Inhibitors, Estrogens, Female, Humans, Isoenzymes, Male, Models, Molecular, Molecular Sequence Data, Phylogeny, Prostatic Neoplasms, Protein Conformation, 17-Hydroxysteroid Dehydrogenases, Molecular Structure, Sequence Alignment, Catalytic Domain
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