Effects of resveratrol on proliferation and apoptosis in rat ovarian theca-interstitial cells
Open accessAbstract
Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and associated with ovarian theca-interstitial (T-I) cell hyperplasia, hyperinsulinemia, systemic inflammation and oxidative stress. This in vitro study tested whether rat T-I cell growth with or without insulin can be altered by resveratrol, a natural polyphenol with anti-carcinogenic, anti-inflammatory, anti-proliferative and antioxidant properties. Rat T-I cells were cultured with and without resveratrol and/or insulin, and the effects on DNA synthesis, number of viable cells and markers of apoptosis were evaluated. Resveratrol alone induced a potent concentration-dependent inhibition of cell growth by inhibiting DNA synthesis, decreasing the number of viable cells and increasing the activity of executioner caspases 3 and 7; these effects of resveratrol counteracted the pro-proliferative and anti-apoptotic effects of insulin. Immunofluorescence analysis of cells incubated with resveratrol showed concentration- and time-dependent morphological changes consistent with apoptosis. The present findings indicate that resveratrol promotes apoptosis to reduce rat T-I cell growth in vitro as well as inhibiting insulin-induced rat T-I cell growth. This suggests a possibility that resveratrol and/or mechanisms mediating its effect may be relevant to the development of novel treatments for PCOS, which is characterized by both excessive ovarian mesenchyma growth and hyperinsulinemia.
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Resveratrol has direct inhibitory effects on ovarian theca-interstitial proliferation and expression of 17α-hydroxylase/C17-20-lyase, demonstrated in in vitro experimental models.
“Changes in androgen levels could have been explained by the direct inhibitory effects of resveratrol on ovarian theca-interstitial proliferation and expression of 17α-hydroxylase/C17-20-lyase, known as the rate-limiting enzyme in androgen biosynthesis, which were demonstrated in in vitro experimental models [139,140].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [139]
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- Duleba AJ, Spaczynski RZ, Olive DL, Behrman HR. Effects of insulin and insulin-like growth factors on proliferation of rat ovarian theca-interstitial cells. Biol Reprod 1997b;56:891 -897.
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“Changes i androgen levels could have been explained by the direct inhibitory effects of resveratrol n ovarian theca-interstitial proliferation and ex ressi f 17 - r x lase/ 17-20-l ase, as t e rate-li iti e z e i a r e i s t esis, ic ere e strate i i itr ex eri e tal els [139,140].”
BackgroundBanaszewska, B., Wrotyńska-Barczyńska, J., Spaczynski, R. Z., Pawelczyk, L., & Duleba, A. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1858 · Cited by 173 · see citing works
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- Authors
- Wong, D. H., Villanueva, J. A., Cress, A. B., & Duleba, A. J.
- Affiliations
- University of California Davis Medical Center (US)
- ORCID
- Wong, D. H.
- Venue
- Molecular Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-12
- Volume
- 16
- Issue
- 4
- Pages
- 251-259
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- PMC
- PMC2834407
- OpenAlex
- W2146390943
- Cited by
- 76
- References
- 60
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 12 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 3
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Human Reproduction (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD050656)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- resveratrol, polycystic ovary syndrome, apoptosis, cell proliferation, insulin, caspase-3, caspase-7, DNA synthesis, oxidative stress, hyperinsulinemia, polyphenols, ovarian dysfunction
- MeSH terms
- Resveratrol, Animals, Cells, Cultured, Female, Stilbenes, Theca Cells, Anticarcinogenic Agents, Apoptosis, Caspases, In Situ Nick-End Labeling, Cell Proliferation, Rats, DNA Fragmentation
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