CoChat
Sign Up
Cited by 406Ovarian function and disordersReproductive Biology and FertilitySexual Differentiation and Disorders

The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome

Nelson, Velen L., Qin, Ke-nan, Rosenfield, Robert L., Wood, Jennifer R., Penning, Trevor M., Legro, Richard S., Strauss, Jerome F., McAllister, Jan M.·2001·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.86.12.8088
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1210/jcem.86.12.8088

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • HSD17B1 is limited to the granulosa cells, where it activates E1 to E2.

    “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

  • A4 can either be secreted or converted to T by AKR1C3 in the theca cells, but the majority of A4 diffuses back to the granulosa cells where it is converted to estrone (E1), estradiol (E2) and E1-sulfate (E1S).

    “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

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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
DOI
10.1210/jcem.86.12.8088
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 › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review