Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries.
Abstract
Anovulation in polycystic ovary syndrome (PCOS) is associated with hyperinsulinemia and insulin resistance, but it has been unclear whether the ovary is insulin resistant in women with PCOS. The aims of this study were, firstly, to determine whether human granulosa cells respond to physiological concentrations of insulin and, secondly, to investigate insulin and gonadotropin interactions in vitro in granulosa cells obtained from normal (N) and polycystic ovaries (PCO). Granulosa cells were incubated with insulin with or without gonadotropins for 48 h. Insulin augmented not only basal production of estradiol and progesterone, but also LH-stimulated steroid accumulation in granulosa cell cultures from N and PCO. Insulin enhanced FSH-stimulated progesterone production by granulosa cells from N and PCO, but the effect on FSH-stimulated estradiol production was variable, ranging from no effect for granulosa cells from N to synergistic for granulosa cells from PCO of anovulatory subjects. Preincubation with insulin for 48 h increased subsequent basal and LH-induced, but not FSH-stimulated, steroid production. These data demonstrate that granulosa cells from PCO respond to insulin despite the association, in vivo, of PCOS with peripheral insulin resistance. Insulin preincubation enhances the subsequent response of human granulosa cells to LH. We propose that in anovulatory women with PCOS, elevated levels of insulin interacting with LH may contribute to the mechanism of anovulation.
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Insulin resistance associated with PCOS seems to be determined also by alterations at the level of insulin receptor signalling, including increased insulin-independent autophosphorylation associated with reduced receptor activity.
“As shown by Dunaif et al., IR associated with PCOS, seems to be determined also by alterations at the level of the insulin receptor signalling. They observed that insulin receptors isolated from fibroblast cultured and skeletal muscle of women with PCOS presented increased insulin-independent autophosphorylation which is associated with reduced receptor activity [24, 25] and can lead to IR.”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [25]
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- Authors
- Willis, D., Mason, H., Gilling-Smith, C., & Franks, S.
- Affiliations
- St Mary's Hospital (GB)
- ORCID
- Franks, S
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1996-01
- Volume
- 81
- Issue
- 1
- Pages
- 302-309
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2171217985
- Cited by
- 371
- References
- 26
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 10 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 7 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 16 · 2012: 11
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- insulin, polycystic ovary syndrome, granulosa cells, follicle-stimulating hormone, luteinizing hormone, insulin resistance, anovulation, estradiol production, progesterone secretion, steroidogenesis, hyperinsulinemia
- MeSH terms
- Adult, Estradiol, Female, Follicle Stimulating Hormone, Granulosa Cells, Humans, Insulin, Luteinizing Hormone, Middle Aged, Ovary, Polycystic Ovary Syndrome, Progesterone
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