Attenuating effect of castration on glomerular injury is age-dependent in unilaterally nephrectomized male...

To clarify a role of sex hormones in greater susceptibility of young rats than adults to the development of focal and segmental glomerulosclerosis (FSGS), we castrated animals at different ages and investigated whether the attenuating effect of castration on FSGS is age-dependent in unilaterally nephrectomized male Sprague-Dawley (SD) rats. At 6 weeks of age, all groups received unilateral right nephrectomy (Nx) and group 2 was simultaneously castrated, while group 1 received a sham operation. Group 3 was castrated at 3 months of age, and group 4 at 6 months of age. Body weight, blood pressure, urinary protein and serum constituents were investigated every 2 months from 4 to 14 months of age. At 6 and 14 months of age, rats were studied morphologically. Castration at 6 weeks of age or at 3 months of age significantly inhibited the compensatory glomerular hypertrophy and hyperfunction with regard to the creatinine clearance as seen in Nx rats at 6 months of age and significantly reduced glomerular injury at the end of the experiment, while castration at 6 months produced neither an inhibitory effect on glomerular hypertrophy nor an attenuating effect on glomerular injury. Serum levels of growth hormone (GH) and somatomedin-C (SmC) were decreased by castration to a greater extent when castrated at younger age. These findings indicated that GH and SmC influenced by male sex hormone seem to play a more important role at younger age than in adults in exerting its effect on glomerular growth, leading somehow to glomerular injury in aging, unilaterally nephrectomized male SD rats.