title: Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis.
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.
authors.affiliation: Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, (C1428DNA) Buenos Aires, Argentina. meresman@dna.uba.ar
authors.forename: Gabriela F
authors.initials: GF
authors.lastname: Meresman
authors.forename: Mariela A
authors.initials: MA
authors.lastname: Bilotas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lombardi
authors.forename: Marta
authors.initials: M
authors.lastname: Tesone
authors.forename: Carlos
authors.initials: C
authors.lastname: Sueldo
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Barañao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism / Q000503:physiopathology*; D004717:Endometrium / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016729:Leuprolide / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix; D016729:Leuprolide