Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende (CS), Italy.
Mol Cell Endocrinol. 2010 May 14;320(1-2):136-44. doi: 10.1016/j.mce.2010.01.035. Epub 2010 Feb 2.
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.
本研究旨在探讨雌激素是否能够直接激活控制大鼠粗线期精母细胞（PS）精子发生的快速信号通路。经典上，雌激素通过与雌激素受体（ERs）alpha 和 beta 结合起作用。最近，已经证明快速雌激素作用也可以通过 G 蛋白偶联受体（GPR）-30 激活。在此，我们证明大鼠 PS 表达 ER alpha、ER beta 和 GPR30。用雌二醇（E2）、选择性 GPR30 激动剂 G1 和选择性 ER alpha 激动剂 PPT 处理 PS，可确定 ERK1/2 的激活，ERK1/2 是 GPR30 信号级联的一部分。E2 和 G1 对 ERK1/2 的激活与 c-Jun 的磷酸化增加相关。在 EGFR 抑制剂 AG1478、ERK 抑制剂 PD98059 和 ER 抑制剂 ICI182780 的存在下，所有处理均未能诱导这些反应。E2 和 G1 下调细胞周期调节剂细胞周期蛋白 A1 和 B1 的 mRNA 表达，而在相同条件下观察到促凋亡因子 Bax 的上调。这些数据表明，E2 通过 ER alpha 和/或 GPR30 激活 PS 中的快速 EGFR/ERK/c-Jun 通路，调节参与细胞增殖和凋亡平衡的基因的表达。
