Cited by 238Estrogen and related hormone effectsSteroid Chemistry and BiochemistryHormonal Regulation and Hypertension

17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: Protein structures, functions, and recent progress in inhibitor development

Marchais-Oberwinkler, Sandrine, Henn, Claudia, Möller, Gabriele, Klein, Tobias, Negri, Matthias, Oster, Alexander, Spadaro, Alessandro, Werth, Ruth +5 more·2011·The Journal of Steroid Biochemistry and Molecular Biology

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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Crossref · 10.1016/j.jsbmb.2010.12.013

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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
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 › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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