Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis.
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.
Meresman
Gabriela F
GF
Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, (C1428DNA) Buenos Aires, Argentina. meresman@dna.uba.ar
Bilotas
Mariela A
MA
Lombardi
Eduardo
E
Tesone
Marta
M
Sueldo
Carlos
C
Barañao
Rosa I
RI
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
D007375:Interleukin-1; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix; D016729:Leuprolide