The GnRH antagonist Antide inhibits apoptosis of preovulatory follicle cells in rat ovary.

PARBORELL F; IRUSTA, GRISELDA; VITALE A; OLGA GONZALEZ; PECCI A; TESONE MARTA

BIOLOGY OF REPRODUCTION (ONLINE)

Año: 2005 vol. 72 p. 659 - 667

1529-7268

Gonadotropin-releasing hormone (GnRH) analogs: agonists (GnRH-a) or antagonists (GnRH-ant) have been widely used to inhibit gonadotropin pituitary release. Besides the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extrapituitary effects, particularly on the rat and human ovary. In the present study, we have evaluated the direct in vivo effects of the GnRH-a: Leuprolide Acetate (LA) and/or the GnRH-ant: Antide (Ant) on ovarian follicular development in prepuberal eCG-treated rats. LA significantly decreased while Ant increased ovarian weight compared to control, however co-injection of both compounds had no effect. In addition, LA increased the number of preantral follicles (PF) and atretic follicles (ATF) and decreased the number of early antral (EAF) and preovulatory follicles (POF). The co-injection of Ant interfered with this LA effect. Ant alone increased the number of POF compared to control. Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PF, EAF and POF; however, Ant prevented this effect. In addition, Ant alone decreased the percentage of apoptotic cells in EAF and POF. Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria while LA induced cytochrome C release. We concluded that Ant inhibits the apoptosis in preovulatory follicles through a decrease of BAX traslocation to mitochondria, suggesting that GnRH may act as a physiological intraovarian modulator factor able to interfere with the follicular development through an increase in apoptotic events mediated by an imbalance among the BCL-2 family members.