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The prepubertal years of type 1 diabetes (DM) appear to be protected from expression of nephropathy and other microvascular complications. Only post-pubertal male rats given the diabetogenic agent streptozocin (STZ) develop renal and glomerular hypertrophy associated with increased expression and activity of transforming growth factor (TGF ). Prepubertal rats do not develop hypertrophy or upregulation of the TGFß system. Given clinical differences between the sexes in the prevalence and rate of progression of many different renal diseases, gonadal steroids seem likely to be involved in these processes. The overall hypothesis of our studies is that androgen synthesis that accompanies puberty contributes to the development of diabetic nephropathy via changes in the renal transforming growth factor ß (TGFß) system. TGFß is widely acknowledged as an important mediator of glomerulosclerosis. The renin-angiotensin system, protein kinase C, and oxidative stress may all contribute to production and activation of TGFß. Androgens have been shown to drive all of these systems, and all of these mechanisms have been implicated in diabetic kidney disease. Techniques used in these studies include western blotting and ELISA; real-time RT-PCR; quantitative histomorphometry; and immunohistochemistry with color image analysis.
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