TY - JOUR
T1 - 17β-Estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ERα
AU - Chimento, Adele
AU - Sirianni, Rosa
AU - Delalande, Christelle
AU - Silandre, Dorothèe
AU - Bois, Camille
AU - Andò, Sebastiano
AU - Maggiolini, Marcello
AU - Carreau, Serge
AU - Pezzi, Vincenzo
N1 - Funding Information:
This work was supported by French Ministry of Education and INRA . We would like to give our thanks to Dr. P. Durand (ENS Lyon) for his scientific comments.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/5
Y1 - 2010/5
N2 - 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) α and β 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 ERα, ERβ and GPR30. Treatment of PS with estradiol (E2), the selective GPR30 agonist G1 and the selective ERα 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 ERα 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.
AB - 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) α and β 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 ERα, ERβ and GPR30. Treatment of PS with estradiol (E2), the selective GPR30 agonist G1 and the selective ERα 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 ERα 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.
KW - Apoptosis
KW - Estrogen
KW - GPR30
KW - Rat
KW - Spermatocytes
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U2 - 10.1016/j.mce.2010.01.035
DO - 10.1016/j.mce.2010.01.035
M3 - Article
C2 - 20132863
AN - SCOPUS:77949570772
SN - 0303-7207
VL - 320
SP - 136
EP - 144
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -