Effect of GnRH analogues on apoptosis and release of interleukin-1  and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis

Gabriela Meresman, Gabriela F Meresman, Mariela A Bilotas, Eduardo Lombardi, Marta Tesone, Carlos Sueldo, Rosa I Barañao
Human Reproduction · 2003 · vol. 18(9) , pp. 1767–1771 · doi:10.1093/humrep/deg356 · PMID:12923126 · W2133958768
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GnRH agonists increased apoptosis and decreased IL-1beta and VEGF release in endometrial cell cultures from endometriosis patients and controls, effects reversed by a GnRH antagonist.

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Abstract

BACKGROUND: The aim of the present study was to evaluate the effect of GnRH analogues on the in-vitro eutopic endometrial cell apoptosis and release of interleukin-1beta (IL-1beta) and vascular endothelial growth factor (VEGF). METHODS: Biopsy specimens of eutopic endometrium obtained from 16 women with untreated endometriosis and 14 controls were studied. Apoptosis, IL-1beta and VEGF release were evaluated in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA) as GnRH agonist, antide as GnRH antagonist, and a combination of both. The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique, and IL-1beta and VEGF concentrations were assessed by using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We found that LA (100 ng/ml) enhanced apoptosis in endometrial cell cultures from endometriosis patients and controls and this effect was reversed by antide at 10(-7) mol/l. IL-1beta and VEGF release was downregulated by LA in cultures from controls and endometriosis patients. The addition of antide 10(-7) mol/l reversed this inhibition. Endometrial cultures treated with antide at 10(-7) mol/l did not show any significant effects compared with basal conditions. CONCLUSIONS: GnRH agonists appear to have a direct effect in endometrial cells cultures, by enhancing the percentage of apoptotic cells and decreasing the release of pro-mitogenic cytokines such as IL-1beta and VEGF.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Apoptosis Endometriosis Endometrium Gonadotropin-Releasing Hormone Interleukin-1 Leuprolide Vascular Endothelial Growth Factor A Apoptosis Case-Control Studies Cells, Cultured Endometriosis Endometriosis Endometrium Endometrium Female Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Humans Interleukin-1 Interleukin-1

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