Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas.
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 beta 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 beta 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 beta cells was detected; however, glucose and insulin serum levels were not significantly different from the controls. The castrated animals presented higher percentages of apoptotic beta 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 beta 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.
Morimoto
S
S
Instituto Nacional de Ciencias Médicas y Nutrición, SZ Vasco de Quiroga 15, Tlalpan 14000, D F México, México.
Mendoza-Rodríguez
C A
CA
Hiriart
M
M
Larrieta
M E
ME
Vital
P
P
Cerbón
M A
MA
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000032:analysis / Q000097:blood; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity*; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors
D000477:Alkylating Agents; D001786:Blood Glucose; D007328:Insulin; D013739:Testosterone; D013311:Streptozocin