The DOI matches its Crossref record; 40 of the 42 references it cites were found in a registry or an index.
The Biochemical Basis for Increased Testosterone Production in Theca Cells Propagated from Patients with Polycystic Ovary Syndrome
Abstract
Ovarian theca cells propagated from patients with polycystic ovary syndrome (PCOS) convert steroid precursors into T more efficiently than normal theca cells. To identify the basis for increased T production by PCOS theca cells, we examined type I-V 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) isoform expression in long-term cultures of theca and granulosa cells isolated from normal and PCOS ovaries. RT-PCR analysis demonstrated that theca cells express type V 17 beta HSD a member of the aldo-keto reductase (AKR) superfamily (17 beta HSDV, AKR1C3), whereas expression of type I, II, and IV 17 beta HSD, which are members of the short-chain dehydrogenase/reductase superfamily, was limited to granulosa cells. Type III 17 beta HSD, the testicular isoform, was not detected in either granulosa or theca cells. Northern and real-time PCR analyses demonstrated that 17 beta HSDV transcripts were not significantly increased in PCOS theca cells compared with normal theca cells. RT-PCR analysis revealed that theca cells also express another AKR, 20 alpha HSD (AKR1C1). Both basal and forskolin-stimulated 20 alpha HSD mRNA levels were increased in PCOS theca cells compared with normal theca cells. However, 17 beta HSD enzyme activity per theca cell was not significantly increased in PCOS, suggesting that neither AKR1C3 nor AKR1C1 contributes to the formation of T in this condition. In contrast, 17 alpha-hydroxylase/C17,20 lyase and 3 beta HSD enzyme activities were elevated in PCOS theca cells, driving increased production of T precursors. These findings indicate that 1) increased T production in PCOS theca cells does not result from dysregulation of "androgenic" 17 beta HSD activity or altered expression of AKRs that may express 17 beta HSD activity; and 2) increased synthesis of T precursors is the primary factor driving enhanced T secretion in PCOS.
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“17β-hydroxysteroid dehydrogenase type 1, HSD17B1, is limited to the granulosa cells, where it activates E1 to E2 (Nelson et al., 2001).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Nelson et al., 2001
In the citing paper
“A4 can either be secreted or converted to T by AKR1C3 in the theca cells (Nelson et al., 2001), but the majority of A4 diffuses back to the granulosa cells where it is converted to estrone (E1), estradiol (E2) and E1-sulfate (E1S) (Miller and Auchus, 2011).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Nelson et al., 2001
Citations
Cites
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Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome
Legro, R. S., Driscoll, D., Strauss, J. F., Fox, J., & Dunaif, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14956 · Cited by 699
Self-citationREVIEW ARTICLE: THE POLYCYSTIC OVARY SYNDROME
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PENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/bj3510067 · Cited by 649
Self-citationMale pseudohermaphroditism caused by mutations of testicular 17β-hydroxysteroid dehydrogenase 3
Geissler, W. M., Davis, D. L., Wu, L., Bradshaw, K. D., Patel, S., Mendonca, B. B., Elliston, K. O., Wilson, J. D., Russell, D. W., & Andersson, S. (1994) · Nature Genetics · doi:10.1038/ng0594-34 · Cited by 570
The Ovarian Androgen Producing Cells: A Review of Structure/Function Relationships1,2
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Nelson, V. L., Legro, R. S., Strauss, J. F., & McAllister, J. M. (1999) · Molecular Endocrinology · doi:10.1210/mend.13.6.0311 · Cited by 556
Self-citationEHRMAN, D. A., Barnes, R. B., & Rosenfield, R. L. (1995) · Endocrine Reviews · doi:10.1210/edrv-16-3-322 · Cited by 498
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The Polycystic Ovary. I. Clinical and Histologic Features
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2 of the 42 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Zawadzki, 1992, Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach, In: Dunaif A, Givens JR, Haseltine FP, Merriam G, eds. Current issues in endocrinology and metabolism. Polycystic ovary syndrome. Boston: Blackwell;, 377
- McAllister, 1993, Human theca interna cells in culture, In: Heindel J, Chapin R, eds. Methods in toxicology. San Diego: Academic Press;, 330
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Items 401–405 of 405
Moreira, M. V., Guerra‐Carvalho, B., Vale-Fernandes, E., Pignatelli, D., Bernardino, R. L., & Monteiro, M. P. (2026) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-026-10055-4
Jensen, L. B., Johannsen, M. L., Bøtkjær, J. A., Veng, A. R., Macklon, K. T., Pedersen, A. F., Styrishave, B., & Kristensen, S. G. (2026) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-026-03983-2
Lv, X.-M., Long, W.-J., Hu, Z.-Y., Shi, M.-Q., Li, X.-Y., Feng, Y.-J., Du, J.-N., Yang, Z.-C., Peng, F., Xing, L.-W., et al. (2026) · Molecules · doi:10.3390/molecules31203633
Leite, A. C. J., & Leite, A. (2004) · Revista Medicina Cutánea Ibero-Latino-Americana
Metadata
- Authors
- Nelson, V. L., Qin, K.-N., Rosenfield, R. L., Wood, J. R., Penning, T. M., Legro, R. S., Strauss, J. F., & McAllister, J. M.
- Affiliations
- Departments of Cellular and Molecular Physiology (V.L.N., J.M.M.), Hershey, Pennsylvania 17033
- Departments of Pediatrics and Medicine, University of Chicago (K.Q., R.L.R.), Chicago, Illinois 60637
- Pennsylvania State University (US)
- University of Pennsylvania (US)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2001-12-01
- Volume
- 86
- Issue
- 12
- Pages
- 5925-5933
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2062389660
- Cited by
- 405
- References
- 42
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 16 · 2021: 33 · 2020: 13 · 2019: 17 · 2018: 16 · 2017: 14 · 2016: 13 · 2015: 15 · 2014: 23 · 2013: 20 · 2012: 24
- FWCI
- 9.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-47015, R01DK047015)
- National Center for Research Resources (RR-00055)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-34449, R01HD033852, HD 33852, HD-39267, HD 07305, U54HD034449, R01HD039267, HD-0118)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- polycystic ovary syndrome, theca cells, testosterone production, 17β-hydroxysteroid dehydrogenase, AKR1C3, AKR1C1, 3β-hydroxysteroid dehydrogenase, steroidogenesis, androgen production, granulosa cells, enzyme activity
- MeSH terms
- Adult, Cells, Cultured, Female, Granulosa Cells, Humans, Hydroxysteroid Dehydrogenases, Isoenzymes, Ovary, Polycystic Ovary Syndrome, Reference Values, RNA, Messenger, Testosterone, Theca Cells, 20-Hydroxysteroid Dehydrogenases, 3-Hydroxysteroid Dehydrogenases, Reverse Transcriptase Polymerase Chain Reaction, 20-alpha-Hydroxysteroid Dehydrogenase
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