Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis

Fertil Steril. 2003 Sep:80 Suppl 2:702-7. doi: 10.1016/s0015-0282(03)00769-6.

Abstract

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.

Design: Prospective study.

Setting: Research institute and clinical fertility center.

Patient(s): Sixteen women with untreated endometriosis and 14 controls.

Intervention(s): 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.

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

Result(s): 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.

Conclusion(s): GnRH-a appears to have a direct effect by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridine Orange / metabolism
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Biopsy
  • Cell Division / drug effects
  • Cell Division / physiology
  • Endometriosis / pathology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Fertility Agents, Female / pharmacology*
  • Gonadotropin-Releasing Hormone / agonists*
  • Hormone Antagonists / pharmacology
  • Humans
  • Leuprolide / pharmacology*
  • Oligopeptides / pharmacology
  • Prospective Studies
  • Thymidine / metabolism
  • Transforming Growth Factor beta / pharmacology

Substances

  • Fertility Agents, Female
  • Hormone Antagonists
  • Oligopeptides
  • Transforming Growth Factor beta
  • Gonadotropin-Releasing Hormone
  • iturelix
  • Leuprolide
  • Acridine Orange
  • Thymidine