17 beta-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ER alpha

Aim of the present study was to investigate whether estrogens were able to directly activate rapid signaling pathways controlling spermatogenesis in rat pachytene spermatocytes (PS). Classically, estrogens act by binding to estrogen receptors (ERs) alpha and beta. Recently, it has been demonstrated...

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Veröffentlicht in:Molecular and cellular endocrinology 2010-05, Vol.320 (1-2), p.136-144
Hauptverfasser: Chimento, Adele, Sirianni, Rosa, Delalande, Christelle, Silandre, Dorothèe, Bois, Camille, Andò, Sebastiano, Maggiolini, Marcello, Carreau, Serge, Pezzi, Vincenzo
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container_end_page 144
container_issue 1-2
container_start_page 136
container_title Molecular and cellular endocrinology
container_volume 320
creator Chimento, Adele
Sirianni, Rosa
Delalande, Christelle
Silandre, Dorothèe
Bois, Camille
Andò, Sebastiano
Maggiolini, Marcello
Carreau, Serge
Pezzi, Vincenzo
description Aim of the present study was to investigate whether estrogens were able to directly activate rapid signaling pathways controlling spermatogenesis in rat pachytene spermatocytes (PS). Classically, estrogens act by binding to estrogen receptors (ERs) alpha and beta. Recently, it has been demonstrated that rapid estrogen action can also be activated through the G-protein-coupled receptor (GPR)-30. Herein, we demonstrated that rat PS express ER alpha, ER beta and GPR30. Treatment of PS with estradiol (E2), the selective GPR30 agonist G1 and the selective ER alpha agonist PPT determined activation of ERK1/2 which are part of GPR30 signaling cascade. ERK1/2 activation in response to E2 and G1 was correlated to an increased phosphorylation of c-Jun. All treatments failed to induce these responses in the presence of EGFR inhibitor AG1478, ERK inhibitor PD98059 and ER inhibitor ICI182780. mRNA expression of cell cycle regulators cyclin A1 and B1 was downregulated by E2 and G1 while an up-regulation of proapoptotic factor Bax was observed in the same conditions. These data demonstrate that E2, working through both ER alpha and/or GPR30, activates in PS the rapid EGFR/ERK/c-Jun pathway, modulating the expression of genes involved in the balance between cellular proliferation and apoptosis.
doi_str_mv 10.1016/j.mce.2010.01.035
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Classically, estrogens act by binding to estrogen receptors (ERs) alpha and beta. Recently, it has been demonstrated that rapid estrogen action can also be activated through the G-protein-coupled receptor (GPR)-30. Herein, we demonstrated that rat PS express ER alpha, ER beta and GPR30. Treatment of PS with estradiol (E2), the selective GPR30 agonist G1 and the selective ER alpha agonist PPT determined activation of ERK1/2 which are part of GPR30 signaling cascade. ERK1/2 activation in response to E2 and G1 was correlated to an increased phosphorylation of c-Jun. All treatments failed to induce these responses in the presence of EGFR inhibitor AG1478, ERK inhibitor PD98059 and ER inhibitor ICI182780. mRNA expression of cell cycle regulators cyclin A1 and B1 was downregulated by E2 and G1 while an up-regulation of proapoptotic factor Bax was observed in the same conditions. 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subjects Activation
Animals
Apoptosis
Apoptosis - drug effects
Cells, Cultured
Cellular
Computer Science
Enzyme Activation - drug effects
Estradiol - pharmacology
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen Receptor beta - genetics
Estrogen Receptor beta - metabolism
Estrogens
Inhibitors
Life Sciences
Male
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Pachytene Stage - drug effects
Pathways
Phenols - pharmacology
Polystyrene resins
Proto-Oncogene Proteins c-jun - metabolism
Pyrazoles - pharmacology
Rats
Rats, Sprague-Dawley
Receptors
Receptors, G-Protein-Coupled - agonists
Receptors, G-Protein-Coupled - antagonists & inhibitors
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Signal Transduction - drug effects
Spermatocytes - cytology
Spermatocytes - drug effects
Spermatocytes - enzymology
Spermatocytes - metabolism
title 17 beta-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ER alpha
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