Effect of Gonadotropin-releasing hormone (GnRH) analogs on the apoptosis and release of IL-1b and VEGF in endometrial cell cultures from patients with endometriosis

MERESMAN GF; BILOTAS M; LOMBARDI E; TESONE M; SUELDO C; BARAÑAO RI

HUMAN REPRODUCTION

Año: 2003 p. 1767 - 1771

0268-1161

BACKGROUND: The aim of the present study was to evaluate the effect of GnRH analogs on the in-vitro eutopic endometrial cell apoptosis and release of IL-1b and VEGF.  METHODS: Biopsy specimens of eutopic endometrium obtained from sixteen women with untreated endometriosis and 14 controls were studied. Apoptosis, IL-1b and VEGF release were evaluated in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA) as GnRH agonist (GnRHa), antide as GnRH antagonist, and a combination of both. Percentage of apoptotic cells was evaluated by the acridine orange - ethidium bromide technique and IL-1b and VEGF concentrations were assessed by using ELISA commercial kits. RESULTS: we found that LA (100 ng/ml) enhanced apoptosis in endometrial cells cultures from endometriosis patients and controls and this effect was reversed by antide at 10-7M. IL-1b and VEGF release was down-regulated by LA in cultures from controls and endometriosis patients. The addition of antide 10-7 M reversed this inhibition. Endometrial cultures treated with antide at 10-7M did not show any significant effects compared to basal conditions. CONCLUSIONS: GnRHa appears to have a direct effect in endometrial cells cultures, by enhancing the percentage of apoptotic cells and decreasing the release of pro-mitogenic cytokines as IL-1b and VEGF. Key words: Apoptosis - Endometriosis - Endometrial cells - GnRH agonist - IL-1b - VEGF.