MAPK/ERK通路
p38丝裂原活化蛋白激酶
活性氧
间质细胞
内科学
胆固醇侧链裂解酶
内分泌学
化学
睾酮(贴片)
信号转导
生物
信使核糖核酸
生物化学
医学
促黄体激素
基因
激素
作者
Aijie Han,Lingyue Zou,Xiaoqin Gan,Yu Li,Fangfang Liu,Xuhong Chang,Xiaotian Zhang,Minmin Tian,Sheng Li,Li Su,Yingbiao Sun
标识
DOI:10.1016/j.toxlet.2018.03.016
摘要
Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways.
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