The protective effect of testosterone on streptozotocin-induced apoptosis in beta cells is sex specific.

Objectives: To investigate the protective role of steroid hormones on streptozotocin (STZ)-induced apoptosis in rat pancreatic beta cells.

Methods: Two sets of experiments were performed. In the first, male rats were orchidectomized and substituted 72 hours later with testosterone, estradiol, or progesterone, and 24 hours later, administered with STZ. Subjects were killed 6 hours later, and apoptosis was determined in sections of the pancreas. In the second experiment, male or female rats were gonadectomized, were further substituted with testosterone, and then administered STZ. Six hours later, the animals were killed, and apoptosis, as well as immunoreactive expression of insulin, catalase, or Cu/Zn superoxide dismutase, was determined in sections of the pancreas. In addition, gonadectomized male or female subjects were substituted with testosterone and administered STZ, and 24 hours later, serum glucose and insulin were measured.

Results: It was found that the cytoprotective effect was only shown in testosterone-treated male rats but not progesterone- or estradiol-treated male rats. In addition, the effect was seen in male rats but not in female rats, and there was an inverse correlation between apoptotic index and antioxidant enzyme immunoreactivity.

Conclusions: The cytoprotective effect of testosterone is sex specific and is related to the induction of antioxidant enzyme activities in pancreatic beta cells.