Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary
Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have been widely used to inhibit gonadotropin pituitary release. Aside from the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extrapituitary effects, particularly on rat and human ovarie...
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todo:paper_00063363_v72_n3_p659_Parborell2023-10-03T14:04:54Z Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary Parborell, F. Irusta, G. Vitale, A. Gonzalez, O. Pecci, A. Tesone, M. Apoptosis Follicle Gonadotropin-releasing hormone Ovary 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid cytochrome c diethylstilbestrol gonadorelin agonist gonadorelin antagonist iturelix leuprorelin protein Bax protein bcl 2 agonist animal cell animal experiment apoptosis article cell count comparative study controlled study cytosol drug effect drug inhibition female gonadotropin release hormone inhibition mitochondrial membrane nonhuman organ weight ovary follicle ovary follicle atresia ovary follicle maturation ovary weight prepuberty priority journal protein family protein synthesis inhibition rat species comparison Animals Apoptosis bcl-2-Associated X Protein Cytochromes c Estrous Cycle Female Gonadotropin-Releasing Hormone Hormone Antagonists Leuprolide Oligopeptides Ovarian Follicle Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Animalia Formicidae Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have been widely used to inhibit gonadotropin pituitary release. Aside from the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extrapituitary effects, particularly on rat and human ovaries. In the present study, we evaluated the direct in vivo effects of the GnRH-a, leuprolide acetate (LA), or the GnRH-ant, Antide (Ant), either singly or together, on ovarian follicular development in prepubertal eCG-treated rats. LA significantly decreased ovarian weight, whereas Ant increased ovarian weight compared with controls; however, coinjection of both compounds had no effect. In addition, LA increased the number of preantral follicles (PFs) and atretic follicles, and decreased the number of early antral follicles (EAFs) and preovulatory follicles (POFs). Coinjection of Ant interfered with this LA effect. Ant alone increased the number of POFs compared with that of controls. Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs; however, Ant prevented this effect. In addition, Ant alone decreased the percentage of apoptotic cells in EAFs and POFs. Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria, whereas LA induced cytochrome C release. We conclude that Ant inhibits apoptosis in preovulatory follicles through a decrease of BAX translocation to mitochondria, suggesting that GnRH may act as a physiological intraovarian modulator factor that is able to interfere with follicular development through an increase in apoptotic events mediated by an imbalance among the BCL-2 family members. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00063363_v72_n3_p659_Parborell |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Apoptosis Follicle Gonadotropin-releasing hormone Ovary 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid cytochrome c diethylstilbestrol gonadorelin agonist gonadorelin antagonist iturelix leuprorelin protein Bax protein bcl 2 agonist animal cell animal experiment apoptosis article cell count comparative study controlled study cytosol drug effect drug inhibition female gonadotropin release hormone inhibition mitochondrial membrane nonhuman organ weight ovary follicle ovary follicle atresia ovary follicle maturation ovary weight prepuberty priority journal protein family protein synthesis inhibition rat species comparison Animals Apoptosis bcl-2-Associated X Protein Cytochromes c Estrous Cycle Female Gonadotropin-Releasing Hormone Hormone Antagonists Leuprolide Oligopeptides Ovarian Follicle Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Animalia Formicidae |
spellingShingle |
Apoptosis Follicle Gonadotropin-releasing hormone Ovary 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid cytochrome c diethylstilbestrol gonadorelin agonist gonadorelin antagonist iturelix leuprorelin protein Bax protein bcl 2 agonist animal cell animal experiment apoptosis article cell count comparative study controlled study cytosol drug effect drug inhibition female gonadotropin release hormone inhibition mitochondrial membrane nonhuman organ weight ovary follicle ovary follicle atresia ovary follicle maturation ovary weight prepuberty priority journal protein family protein synthesis inhibition rat species comparison Animals Apoptosis bcl-2-Associated X Protein Cytochromes c Estrous Cycle Female Gonadotropin-Releasing Hormone Hormone Antagonists Leuprolide Oligopeptides Ovarian Follicle Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Animalia Formicidae Parborell, F. Irusta, G. Vitale, A. Gonzalez, O. Pecci, A. Tesone, M. Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
topic_facet |
Apoptosis Follicle Gonadotropin-releasing hormone Ovary 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid cytochrome c diethylstilbestrol gonadorelin agonist gonadorelin antagonist iturelix leuprorelin protein Bax protein bcl 2 agonist animal cell animal experiment apoptosis article cell count comparative study controlled study cytosol drug effect drug inhibition female gonadotropin release hormone inhibition mitochondrial membrane nonhuman organ weight ovary follicle ovary follicle atresia ovary follicle maturation ovary weight prepuberty priority journal protein family protein synthesis inhibition rat species comparison Animals Apoptosis bcl-2-Associated X Protein Cytochromes c Estrous Cycle Female Gonadotropin-Releasing Hormone Hormone Antagonists Leuprolide Oligopeptides Ovarian Follicle Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Animalia Formicidae |
description |
Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have been widely used to inhibit gonadotropin pituitary release. Aside from the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extrapituitary effects, particularly on rat and human ovaries. In the present study, we evaluated the direct in vivo effects of the GnRH-a, leuprolide acetate (LA), or the GnRH-ant, Antide (Ant), either singly or together, on ovarian follicular development in prepubertal eCG-treated rats. LA significantly decreased ovarian weight, whereas Ant increased ovarian weight compared with controls; however, coinjection of both compounds had no effect. In addition, LA increased the number of preantral follicles (PFs) and atretic follicles, and decreased the number of early antral follicles (EAFs) and preovulatory follicles (POFs). Coinjection of Ant interfered with this LA effect. Ant alone increased the number of POFs compared with that of controls. Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs; however, Ant prevented this effect. In addition, Ant alone decreased the percentage of apoptotic cells in EAFs and POFs. Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria, whereas LA induced cytochrome C release. We conclude that Ant inhibits apoptosis in preovulatory follicles through a decrease of BAX translocation to mitochondria, suggesting that GnRH may act as a physiological intraovarian modulator factor that is able to interfere with follicular development through an increase in apoptotic events mediated by an imbalance among the BCL-2 family members. |
format |
JOUR |
author |
Parborell, F. Irusta, G. Vitale, A. Gonzalez, O. Pecci, A. Tesone, M. |
author_facet |
Parborell, F. Irusta, G. Vitale, A. Gonzalez, O. Pecci, A. Tesone, M. |
author_sort |
Parborell, F. |
title |
Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
title_short |
Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
title_full |
Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
title_fullStr |
Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
title_full_unstemmed |
Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
title_sort |
gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary |
url |
http://hdl.handle.net/20.500.12110/paper_00063363_v72_n3_p659_Parborell |
work_keys_str_mv |
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