Disparate effects of castration on renal structure and function in the streptozotocin diabetic rat.

Abstract

Diabetic children are protected from the complications of diabetes until puberty, suggesting the involvement of a hormonal mechanism. In order to investigate the contribution of sex steroids to the development of diabetic nephropathy, castrated Wistar-Kyoto rats were made diabetic with streptozotocin and compared with intact diabetic rats. In intact rats, 32 weeks of diabetes resulted in hyperfiltration (p = 0.0001) and a marked increase in albuminuria (control, 1.3 x/divided by 1.3 vs diabetes intact, 11.8 x/divided by 1.3 mg/day, p < 0.001). Concomitant structural changes included glomerular basement membrane thickening (diabetes, 199.2 +/- 7.9 vs control, 175.9 +/- 3.9 nm, p = 0.02) and increased mesangial volume (diabetes, 194 +/- 14 vs control, 129 +/- 20 microns 3, p = 0.02). Although castration resulted in blood pressure lowering of 12 mmHg (p = 0.0003), albuminuria increased to the same extent in intact and castrated diabetic rats (castrated diabetic 10.5 x/divided by 1.3 mg/day). Glomerular filtration rate was lower in castrated rats than in intact rats prior to induction of diabetes, but increased similarly with induction of diabetes. Castrated diabetic rats had increased mesangial volume (castrated diabetic, 213 +/- 20 microns 3), but glomerular basement membrane thickness was lower than in intact diabetic rats (castrated diabetic, 179.5 +/- 4.5 nm). Thus, there is a dissociation between basement membrane thickening and albuminuria in this model of diabetic kidney disease. The mechanism of action of castration on glomerular function and structure remains to be elucidated but may relate to indirect effects such as reduction of blood pressure or renal polyol accumulation or a direct effect of sex steroids.