The DOI matches its Crossref record; 51 of the 54 references it cites were found in a registry or an index.
Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype
Open accessAbstract
Polycystic ovary syndrome (PCOS), characterized by increased ovarian androgen biosynthesis, anovulation, and infertility, affects 5-7% of reproductive-age women. Genome-wide association studies identified PCOS candidate loci that were replicated in subsequent reports, including DENND1A, which encodes a protein associated with clathrin-coated pits where cell-surface receptors reside. However, these studies provided no information about functional roles for DENND1A in the pathogenesis of PCOS. DENND1A protein was located in the cytoplasm as well as nuclei of theca cells, suggesting a possible role in gene regulation. DENND1A immunostaining was more intense in the theca of PCOS ovaries. Using theca cells isolated and propagated from normal cycling and PCOS women, we found that DENND1A variant 2 (DENND1A.V2) protein and mRNA levels are increased in PCOS theca cells. Exosomal DENND1A.V2 RNA was significantly elevated in urine from PCOS women compared with normal cycling women. Forced overexpression of DENND1A.V2 in normal theca cells resulted in a PCOS phenotype of augmented CYP17A1 and CYP11A1 gene transcription, mRNA abundance, and androgen biosynthesis. Knock-down of DENND1A.V2 in PCOS theca cells reduced androgen biosynthesis and CYP17A1 and CYP11A1 gene transcription. An IgG specific to DENND1A.V2 also reduced androgen biosynthesis and CYP17 and CYP11A1 mRNA when added to the medium of cultured PCOS theca cells. We conclude that the PCOS candidate gene, DENND1A, plays a key role in the hyperandrogenemia associated with PCOS. These observations have both diagnostic and therapeutic implications for this common disorder.
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“Overexpression of the alternative spliced variant, DENND1A.V2, of this gene recapitulated a PCOS phenotype in cultured theca cells obtained from normal women, indicating a role for this variant in the excessive theca cell androgen production [27].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [27]
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Cites
A new technique for the assay of infectivity of human adenovirus 5 DNA
Graham, F. L., & van der Eb, A. J. (1973) · Virology · doi:10.1016/0042-6822(73)90341-3 · Cited by 9,302
(2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.10.004 · Cited by 9,050
The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2004) · Human Reproduction · doi:10.1093/humrep/deh098 · Cited by 6,138
Rab GTPases as coordinators of vesicle traffic
Stenmark, H. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2728 · Cited by 3,413
Azziz, R., Carmina, E., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H. F., Futterweit, W., Janssen, O. E., Legro, R. S., Norman, R. J., Taylor, A. E., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0178 · Cited by 2,143
Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., & Welt, C. K. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2350 · Cited by 1,919
Polycystic ovary syndrome: etiology, pathogenesis and diagnosis
Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G., & Azziz, R. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.217 · Cited by 1,488
Chen, Z.-J., Zhao, H., He, L., Shi, Y., Qin, Y., Shi, Y., Li, Z., You, L., Zhao, J., Liu, J., et al. (2011) · Nature Genetics · doi:10.1038/ng.732 · Cited by 782
Stenmark, H., & Olkkonen, V. M. (2001) · Genome biology · doi:10.1186/gb-2001-2-5-reviews3007 · Cited by 740
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
Research works printed but not linked: 2
- J Zawadzki, A Dunaif Diagnostic Criteria for Polycystic Ovary Syndrome: Towards a Rational Approach (Blackwell Scientific, Boston), pp. 377–384 (1992).
- J McAllister, E Simpson, Human theca interna cells in culture. Methods in Toxicology, eds JJ Heindel, RE Chapin (Academic, San Diego), pp. 330–339 (1993).
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Marie, C. (2024) · theses.fr (ABES) · doi:10.70675/1310af87z3c5ez4c52zad31z9af8ec853cee
Liznevalizneva, D., Atabiekovi, I., & Azzizricardo, R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-21477-6.00612-x
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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
“V2 in theca cells from PCOS made them revert to a normal phenotype [137].”
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Metadata
- Authors
- McAllister, J. M., Modi, B., Miller, B. A., Biegler, J., Bruggeman, R., Legro, R. S., & Strauss, J. F.
- Affiliations
- Pennsylvania State University (US)
- Virginia Commonwealth University (US)
- Departments of aPathology and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-03-31
- Volume
- 111
- Issue
- 15
- Pages
- E1519-27
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3992676
- OpenAlex
- W1984174412
- Cited by
- 250
- References
- 54
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 32 · 2023: 13 · 2022: 19 · 2021: 25 · 2020: 24 · 2019: 19 · 2018: 16 · 2017: 15 · 2016: 25 · 2015: 20 · 2014: 9
- FWCI
- 27.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Virginia Commonwealth University
- National Institutes of Health (UL1TR000127, U54HD344449)
- U.S. Public Health Service (UL1T000058, UL1T0000127)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD33852, U54HD344449, R01HD033852, R01HD058300)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, DENND1A, theca cells, androgen production, CYP17A1, CYP11A1, hyperandrogenemia, exosomal RNA, urinary biomarkers, clathrin-coated pits, gene overexpression
- MeSH terms
- Analysis of Variance, Androgens, Cholesterol Side-Chain Cleavage Enzyme, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin G, Immunohistochemistry, Polycystic Ovary Syndrome, Steroid 17-alpha-Hydroxylase, Theca Cells, Hyperandrogenism, Protein Isoforms, Guanine Nucleotide Exchange Factors, Death Domain Receptor Signaling Adaptor Proteins, Genome-Wide Association Study, Real-Time Polymerase Chain Reaction
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