Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Stress. 2012 Jan;15(1):74-84. doi: 10.3109/10253890.2011.585188. Epub 2011 Jul 26.
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.
应激通过高水平的糖皮质激素（应激的标志）破坏男性生殖轴的内分泌信号。我们之前的工作表明，外源性糖皮质激素的应激水平可诱导大鼠睾丸间质细胞凋亡，而睾丸间质细胞是睾酮的主要来源。本研究旨在探讨应激是否会在体内诱导大鼠睾丸间质细胞凋亡，如果是，该过程是否是糖皮质激素直接作用的结果。在慢性应激大鼠模型中，血清皮质酮浓度显著升高，而血清睾酮降低。应激大鼠的凋亡性间质细胞频率也增加。接受慢性应激的肾上腺切除术大鼠的血清睾酮水平升高，而间质细胞凋亡频率没有增加。研究表明，糖皮质激素诱导的间质细胞凋亡是由糖皮质激素受体（GRs）介导的，GRs 从细胞质转位到细胞核。腺病毒微 RNA 体外诱导的 GR 表达下调减轻了皮质酮诱导的间质细胞凋亡增加。这些结果表明，应激引起的皮质酮分泌增加导致大鼠体内睾丸间质细胞凋亡，从而减少睾酮合成。
