Abstract:
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-1 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. © 2007 Wiley-Liss, Inc.
Registro:
Documento: |
Artículo
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Título: | Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs |
Autor: | Parborell, F.; Irusta, G.; Celín, A.R.; Tesone, M. |
Filiación: | Instituto de Biología Y Mediana Experimental (IBYME)-CONICET, Departamento de Fisiología, Universidad de Buenos Aires, Buenos Aires, Argentina Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina Institute de Biologia Y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina
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Palabras clave: | Angiogenesis; Apoptosis; GnRH-I analogs; Ovary; angiopoietin receptor; caspase 3; iturelix; leuprorelin; vasculotropin A; vasculotropin receptor 2; angiogenesis; apoptosis; article; controlled study; enzyme activity; female; immunochemistry; in vivo study; nonhuman; ovary; ovary follicle; priority journal; protein expression; rat; Angiopoietin-1; Animals; Apoptosis; Caspase 3; Enzyme Activation; Female; Gonadotropin-Releasing Hormone; Injections, Subcutaneous; Leuprolide; Neovascularization, Physiologic; Oligopeptides; Ovarian Follicle; Ovary; Rats; Rats, Sprague-Dawley; Receptor, TIE-2; Structure-Activity Relationship; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Rattus |
Año: | 2008
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Volumen: | 75
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Número: | 4
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Página de inicio: | 623
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Página de fin: | 631
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DOI: |
http://dx.doi.org/10.1002/mrd.20806 |
Título revista: | Molecular Reproduction and Development
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Título revista abreviado: | Mol. Reprod. Dev.
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ISSN: | 1040452X
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CODEN: | MREDE
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CAS: | caspase 3, 169592-56-7; iturelix, 112568-12-4; leuprorelin, 53714-56-0, 74381-53-6; vasculotropin A, 489395-96-2; Angiopoietin-1; Caspase 3, EC 3.4.22.-; Gonadotropin-Releasing Hormone, 33515-09-2; iturelix, 112568-12-4; Leuprolide, 53714-56-0; Oligopeptides; Receptor, TIE-2, EC 2.7.1.112; Vascular Endothelial Growth Factor A; vascular endothelial growth factor A, rat; Vascular Endothelial Growth Factor Receptor-2, EC 2.7.1.112
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1040452X_v75_n4_p623_Parborell |
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Citas:
---------- APA ----------
Parborell, F., Irusta, G., Celín, A.R. & Tesone, M.
(2008)
. Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs. Molecular Reproduction and Development, 75(4), 623-631.
http://dx.doi.org/10.1002/mrd.20806---------- CHICAGO ----------
Parborell, F., Irusta, G., Celín, A.R., Tesone, M.
"Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs"
. Molecular Reproduction and Development 75, no. 4
(2008) : 623-631.
http://dx.doi.org/10.1002/mrd.20806---------- MLA ----------
Parborell, F., Irusta, G., Celín, A.R., Tesone, M.
"Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs"
. Molecular Reproduction and Development, vol. 75, no. 4, 2008, pp. 623-631.
http://dx.doi.org/10.1002/mrd.20806---------- VANCOUVER ----------
Parborell, F., Irusta, G., Celín, A.R., Tesone, M. Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs. Mol. Reprod. Dev. 2008;75(4):623-631.
http://dx.doi.org/10.1002/mrd.20806