Gonadotropins mediate DNA synthesis and protection from spontaneous cell death in human ovarian surface epithelium
R J Edmondson1, J M Monaghan, B R Davies
1Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, Tyne and Wear NE9 6SX, UK. richard.edmondson@ghnt.nhs.uk
Abstract:
Gonadotropins have been implicated in the development of epithelial ovarian cancers. These tumors are derived from ovarian surface epithelium (OSE). The purpose of this study was to determine the effects of these hormones on DNA synthesis and spontaneous cell death in primary cultures of OSE and three immortalized OSE cultures. Primary cultures of OSE cells were generated from the ovaries of women with benign disease. The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on DNA synthesis and cell death were determined using [(3)H]thymidine incorporation and JAM assays. Significant inductions of DNA synthesis were demonstrated with LH in 4/12 (33%) primary cultures of OSE and 2/3 OSE cell lines and with FSH in 4/11 (36%) primary cultures of OSE and 2/3 OSE cell lines. A significant protection from cell death was also observed in the presence of FSH in 2/4 primary cultures of OSE and 1/3 OSE cell lines and in the presence of LH in 1/4 primary cultures of OSE and 2/3 OSE cell lines. The results indicate that while gonadotropins have the potential to induce cell proliferation and protect from cell death in OSE cells in vitro, their effects are variable in OSE cells from different women.
Insights
Gonadotropins like follicle-stimulating hormone (FSH) and luteinizing hormone (LH) can stimulate ovarian surface epithelium (OSE) cell DNA synthesis and protect against cell death in laboratory studies. However, their effects on OSE cells vary between individuals.
Area of Science:
- Reproductive Endocrinology
- Gynecologic Oncology
- Cell Biology
Background:
- Epithelial ovarian cancers originate from ovarian surface epithelium (OSE).
- Gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are suspected to play a role in ovarian cancer development.
- Understanding the effects of gonadotropins on OSE cells is crucial for investigating ovarian cancer pathogenesis.
Purpose of the Study:
- To investigate the impact of FSH and LH on DNA synthesis in primary OSE cultures and immortalized OSE cell lines.
- To assess the influence of FSH and LH on spontaneous cell death in OSE cells.
- To determine the variability of gonadotropin effects across different OSE cell samples.
Main Methods:
- Primary OSE cell cultures were established from women with benign gynecologic conditions.
- Immortalized OSE cell lines were utilized for comparative analysis.
- [(3)H]thymidine incorporation assays measured DNA synthesis.
- JAM assays were employed to quantify spontaneous cell death.
Main Results:
- Both FSH and LH significantly induced DNA synthesis in a proportion of primary OSE cultures and OSE cell lines.
- FSH demonstrated significant protection from cell death in some primary OSE cultures and OSE cell lines.
- LH also provided significant protection from cell death in a subset of OSE cell lines and primary cultures.
- The observed effects of gonadotropins on OSE cells exhibited considerable variability.
Conclusions:
- Gonadotropins possess the capacity to stimulate proliferation and inhibit cell death in OSE cells in vitro.
- The response of OSE cells to gonadotropins is heterogeneous, varying between cell cultures from different individuals.
- These findings suggest a complex role for gonadotropins in OSE biology with implications for ovarian cancer research.
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