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¹ Instituto Nacional de Ciencias Médicas y Nutrición, SZ Vasco de Quiroga 15, Tlalpan 14000, D F México, México
² Facultad de Química and
³ Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Coyoacan 04510, D F México, México

(Requests for offprints should be addressed to S Morimoto, Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14000, DF México, México; Email sumimor{at}yahoo.com)

Beta-cell apoptosis is responsible for the development of insulin-dependent diabetes mellitus in the streptozotocin (STZ) rat model. It has been demonstrated that steroid hormones possess antioxidant and protective antiapoptotic effects in many tissues. The aim of the present study was to investigate the early apoptotic damage induced by STZ in rat pancreas, and the effect of testosterone in preventing apoptosis of pancreatic ß cells. Intact and castrated adult male Wistar rats were subjected to a unique injection of STZ 60 mg/kg (body weight) in citrate buffer, and the kinetics of apoptosis in ß cells was assessed. Insulin and glucose were measured by RIA and a glucometer respectively, and in pancreatic tissue by immunohistochemistry. At 6 h after STZ injection, a marked increase in apoptotic ß cells was detected; however, glucose and insulin serum levels were not significantly different from the controls. The castrated animals presented higher percentages of apoptotic ß cells (65.75 ± 5.42%) than intact males (20.6 ± 4.38%) and castrated, testosterone-substituted males (30.66 ± 1.38%). The decrease in apoptotic ß cells induced by testosterone was reversed by the antiandrogen flutamide (67.69 ± 3.45%). The overall results indicate that early apoptotic damage produced by STZ in castrated animals was reversed by testosterone, suggesting that this hormone exerts a natural protective effect in rat pancreas. This effect could help to explain some sexual differences in diabetes mellitus incidence in man, reinforcing the idea that new approaches in steroid hormone therapies should be considered for treatment of this disease.

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