Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs

An adequate vascular supply is important to provide endocrine and paracrine signals during follicular development. We evaluated the direct in vivo effects of both the GnRH‐agonist Leuprolide acetate (LA) and the GnRH‐antagonist Antide (Ant) on the expression of VEGF‐A and ANPT‐1 and their receptors...

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Veröffentlicht in:Molecular reproduction and development 2008-04, Vol.75 (4), p.623-631
Hauptverfasser: Parborell, Fernanda, Irusta, Griselda, Rodríguez Celín, Alejandra, Tesone, Marta
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Sprache:eng
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Zusammenfassung:An adequate vascular supply is important to provide endocrine and paracrine signals during follicular development. We evaluated the direct in vivo effects of both the GnRH‐agonist Leuprolide acetate (LA) and the GnRH‐antagonist Antide (Ant) on the expression of VEGF‐A and ANPT‐1 and their receptors in ovarian follicles from prepubertal eCG‐treated rats. We also examined whether the changes observed in apoptosis by GnRH‐I analogs have an effect on the caspase cascade. LA significantly decreased the levels of VEGF‐A, its receptor Flk‐1, and ANPT‐1 when compared to controls, while the co‐injection of Ant interfered with this effect. No changes were observed in the levels of Tie‐2 after treatment with these analogs. When we measured the follicular content of caspase‐3 protein, we observed that LA significantly increased the level of the active form. The co‐injection of Ant interfered with this effect and Ant alone significantly decreased caspase‐3 cleavage. IHC analyses corroborated these data. Notably, while LA increased caspase‐3 activity levels, Ant decreased them when compared to controls. In follicles obtained from LA‐treated rats, cleavage of PARP (a substrate of caspase‐3) from the intact 113‐kDa protein showed a significant enhancement in an 85‐kDa fragment. The co‐injection of Ant interfered with this effect. Ant alone significantly decreased PARP cleavage as compared to controls. We conclude that the decrease in VEGF‐A, its receptor Flk‐1/KDR, and ANPT‐1 produced by the administration of GnRH‐I agonist is one of the mechanisms involved in ovarian cell apoptosis. This suggests an intraovarian role of an endogenous GnRH‐like peptide in gonadotropin‐induced follicular development. Mol. Reprod. Dev. 75: 623–631, 2008. © 2007 Wiley‐Liss, Inc.
ISSN:1040-452X
1098-2795
DOI:10.1002/mrd.20806