Stress induces glucocorticoid-mediated apoptosis of rat Leydig cells in vivo
Stress induces glucocorticoid-mediated apoptosis of rat Leydig cells in vivo
复制标题
应激诱导体内糖皮质激素介导的大鼠 Leydig 细胞凋亡
DOI：
10.3109/10253890.2011.585188
复制
发表时间：
2012-01-01
影响因子：
2.3
通讯作者：
Zhang, Ping
中科院分区：
文献类型：
--
作者：
Chen, Yong;Wang, Qian;Zhang, Ping
压力可以通过高浓度的糖皮质激素破坏男性生殖轴的内分泌信号，这是压力的标志。我们以前的工作表明，外源性糖皮质激素的应激水平可以诱导大鼠睾丸间质细胞的凋亡，这是睾酮的主要来源。本研究的目的是调查是否压力可以诱导大鼠睾丸间质细胞在体内的凋亡，如果是这样的话，这个过程是否是糖皮质激素的直接作用的结果。在慢性应激大鼠模型中，血清皮质酮浓度显着增加，而血清睾酮降低。应激大鼠睾丸间质细胞凋亡的频率也增加。肾上腺切除大鼠慢性应激表现出血清睾酮升高，而睾丸间质细胞的凋亡频率并没有增加。已经确定糖皮质激素诱导的Leydig细胞凋亡是由糖皮质激素受体（GR）介导的，其从细胞质易位到细胞核。腺病毒microRNA在体外诱导GR表达下调，减轻皮质酮诱导的Leydig细胞凋亡增加。这些结果表明，应激诱导的皮质酮分泌增加导致大鼠体内Leydig细胞凋亡，从而降低睾酮的合成。
Stress can disrupt endocrine signalling in the male reproductive axis through high concentrations of glucocorticoids, the hallmark of stress. Our previous work revealed that a stress level of exogenous glucocorticoids could induce apoptosis of rat Leydig cells, which are the primary source of testosterone. The aim of this study was to investigate whether stress can induce apoptosis in rat Leydig cells in vivo and, if so, whether the process is the result of a direct effect of glucocorticoids. In a chronically stressed rat model, serum corticosterone concentration was increased significantly whereas serum testosterone was decreased. The frequency of apoptotic Leydig cells in stressed rats was also increased. Adrenalectomised rats subjected to chronic stress showed an elevated serum testosterone, while the apoptotic frequency of Leydig cells was not increased. It was established that glucocorticoid-induced Leydig cell apoptosis is mediated by glucocorticoid receptors (GRs), which translocate from cytoplasm to nucleus. Adenovirus microRNA-induced downregulation of GR expression in vitro alleviated the corticosterone-induced increase in apoptosis of Leydig cells. These results indicate that the stress-induced increase in corticosterone secretion resulted in apoptosis in rat Leydig cells in vivo, and thereby decreased testosterone synthesis.