Stress induces glucocorticoid-mediated apoptosis of rat Leydig cells in vivo

Abstract

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.

Keywords::

• Adenovirus microRNA
• adrenalectomy
• apoptosis
• glucocorticoid receptor
• Leydig cell
• testosterone

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant numbers 30570681, 214503 and 31000662). Technical assistance by Mr Qiang-Su Guo, from the Department of Histology and Embryology, and the staff from the Department of Cell Biology at Shanghai Jiao Tong University School of Medicine are greatly appreciated.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.