Regulation of ovarian angiogenesis and apoptosis by GnRH-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...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2008 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/25980 |
| Acceso en línea: | http://hdl.handle.net/11336/25980 |
| Access Level: | acceso abierto |
| Palabra clave: | Ovary Angiogenesis Apoptosis Gnrh https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| Sumario: | 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. |
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