Genes and proteins of the alternative steroid backdoor pathway for dihydrotestosterone synthesis are expressed in the human ovary and seem enhanced in the polycystic ovary syndrome
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Recently, dihydrotestosterone biosynthesis through the backdoor pathway has been implicated for the human testis in addition to the classic pathway for testosterone (T) synthesis. In the human ovary, androgen precursors are crucial for estrogen synthesis and hyperandrogenism in pathologies such as the polycystic ovary syndrome is partially due to ovarian overproduction. However, a role for the backdoor pathway is only established for the testis and the adrenal, but not for the human ovary. To investigate whether the backdoor pathway exists in normal and PCOS ovaries, we performed specific gene and protein expression studies on ovarian tissues. We found aldo-keto reductases (AKR1C1-1C4), 5α-reductases (SRD5A1/2) and retinol dehydrogenase (RoDH) expressed in the human ovary, indicating that the ovary might produce dihydrotestosterone via the backdoor pathway. Immunohistochemical studies showed specific localization of these proteins to the theca cells. PCOS ovaries show enhanced expression, what may account for the hyperandrogenism.
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The presence of SRD5A1, AKR1C2, AKR1C4 and HSD17B6 has been demonstrated for ovarian theca cells and some of those are required for the functioning of the backdoor pathway, which produces DHT by-passing DHEA, A4 and T.
“The presence of steroid 5α-reductase type 1 (SRD5A1), aldo-keto reductase 1C2 (AKR1C2), aldo-keto reductase 1C4 (AKR1C4) and 17β-hydroxysteroid dehydrogenase type 6 (HSD17B6) has also been demonstrated for ovarian theca cells and some of those are required for the functioning of the backdoor pathway, which produces DHT by-passing DHEA, A4 and T, (section 5.3), (Marti et al., 2017).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Marti et al., 2017
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WOMEN IN REPRODUCTIVE SCIENCE: Reproduction down under
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Self-citationEtiopatogenesis, Diagnostics and Treatment of Polycystic Ovarian Syndrome in Adolescents
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The Recent Advances in Biomarkers in Endocrinological Diseases: A Narrative Review
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- Authors
- Marti, N., Galván, J. A., Pandey, A. V., Trippel, M., Tapia, C., Müller, M., Perren, A., & Flück, C. E.
- Affiliations
- University of Bern (CH)
- Corresponding author
- Flück, Christa E.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 441
- Pages
- 116-123
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2493373567
- Cited by
- 76
- References
- 26
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 7 · 2023: 12 · 2022: 6 · 2021: 3 · 2020: 9 · 2019: 12 · 2018: 4 · 2017: 11 · 2016: 2
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 342 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular and Cellular Endocrinology (acceptedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030-146127)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- polycystic ovary syndrome, human ovary, aldo-keto reductase, 5α-reductase, retinol dehydrogenase, theca cells, ovarian hyperandrogenism, androgen precursors
- MeSH terms
- Adolescent, Adrenal Glands, Adult, Child, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Ovary, Polycystic Ovary Syndrome, Dihydrotestosterone, Testis, Biosynthetic Pathways, Young Adult
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