Insulin and insulin-like growth factors inhibit and luteinizing hormone augments ovarian theca-interstitial cell apoptosis
Abstract
Theca-interstitial (T-I) cells play a fundamental role in the control of ovarian function. Steroidogenic activity and growth of the T-I cells are regulated by many paracrine and endocrine factors. However, little is known about the mechanisms controlling T-I death. In an in vitro model of apoptosis, purified rat T-I cells were cultured for 24 h with serum and subsequently for up to an additional 24 h with serum or in serum-free medium with or without insulin, insulin-like growth factors (IGF-I and IGF-II) and LH or 8-bromo-cyclic AMP (8Br-cAMP). Apoptosis was identified by histological assessment of nuclear morphology and by detection of internucleosomal cleavage and quantified by determination of [alpha32P]-dideoxy-ATP 3'-end labeling of low molecular weight DNA. Serum withdrawal resulted in nuclear condensation and fragmentation into apoptotic bodies of T-I cells and led to pronounced DNA cleavage. Insulin (10 nM) protected T-I cells from apoptosis, reducing DNA fragmentation by 39 +/- 8% compared to serum-free controls. IGF-I (10 nM) and IGF-II (10 nM) had comparable antiapoptotic effects, decreasing DNA fragmentation by 55 +/- 9% and 37 +/- 14%, respectively. In contrast, LH (100 ng/ml) and 8Br-cAMP (1 mM) augmented the pro-apoptotic effect of serum withdrawal, increasing DNA fragmentation by 85 +/- 55% and 72 +/- 42%, respectively. The antiapoptotic effects of insulin and IGFs and the pro-apoptotic effect of LH, acting via the cAMP system, may be important in the maintenance of T-I homeostasis. Moreover, excessive levels of insulin and free IGFs may lead to T-I cell hyperplasia characteristic of conditions such as polycystic ovary syndrome.
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In polycystic ovarian syndrome, insulin has a stimulatory and anti-apoptotic effect on theca cells, resulting in hyperplasia of these cells.
“Furthermore, in PCOS, insulin has a stimulatory and anti-apoptotic effect on the theca cells, resulting in the hyperplasia of these cells [81].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [81]
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- Authors
- Spaczynski, R. Z., Tilly, J. L., Mansour, A., & Duleba, A. J.
- ORCID
- Tilly, Jonathan L.
- Venue
- MHR: Basic science of reproductive medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-05-01
- Volume
- 11
- Issue
- 5
- Pages
- 319-324
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- OpenAlex
- W2169877690
- Cited by
- 24
- References
- 44
- Citations by year
- 2021: 1 · 2020: 1 · 2018: 1 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd040207-04)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD40207)
- 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 › Cell death mechanisms and regulation
- Keywords
- theca-interstitial cells, apoptosis, insulin, insulin-like growth factor I, insulin-like growth factor II, luteinizing hormone, cyclic AMP, serum deprivation, DNA fragmentation, ovarian steroidogenesis, polycystic ovary syndrome, cell hyperplasia
- MeSH terms
- Animals, Cells, Cultured, Female, Insulin, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Luteinizing Hormone, Theca Cells, 8-Bromo Cyclic Adenosine Monophosphate, Rats, Sprague-Dawley, Apoptosis, Rats
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