Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis.
OBJECTIVE
There is growing evidence that suggests a direct action of gonadotropin-releasing hormone agonist (GnRH-a) on endometrial growth. Consequently, our purpose was to evaluate the effect of GnRH-a on in vitro eutopic endometrial cell growth and apoptosis.


METHODS
Prospective study.


METHODS
Research institute and clinical fertility center.


METHODS
Sixteen women with untreated endometriosis and 14 controls.


METHODS
Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA), antide, and a combination of both.


METHODS
The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique; cell proliferation was assessed by (3)H-thymidine incorporation.


RESULTS
Leuprolide acetate (LA) (100 ng/mL) enhanced apoptosis in endometrial cultures from patients with endometriosis and controls, and this effect was reversed by antide 10(-7)M. Cell proliferation was down-regulated by LA at 1, 10, and 100 ng/mL in cultures from women without and with endometriosis. The addition of antide 10(-7)M reversed this inhibition.


CONCLUSIONS
GnRH-a appears to have a direct effect by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells.
D000165:Acridine Orange / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001706:Biopsy; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004715:Endometriosis / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D011446:Prospective Studies; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D009842:Oligopeptides; D016212:Transforming Growth Factor beta; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix; D016729:Leuprolide; D000165:Acridine Orange; D013936:Thymidine