SEX DIFFERENCE IN PROGRESSION OF ADRIAMYCIN-INDUCED NEPHROPATHY IN RATS

To clarify the pathogenesis of focal-segmental glomerulosclerosis, we investigated the sex-related difference and the effect of castration i n Adriamycin (ADR) induced nephropathy of Sprague-Dawley rats. At 5 we eks of age, group 1 female and group 2 male rats were sham operated, a nd group 3 male rats were castrated. ADR 2 mg/kg was intravenously adm inistered to all rats at 8 weeks of age twice at a 20-day interval. Bo dy weight, blood pressure, urinary protein, and serum constituents wer e investigated every 4 weeks, 4-20 weeks after the second ADR injectio n. Each group was studied morphologically 12 and 20 weeks after the se cond ADR injection. ADR induced massive proteinuria in male rats, wher eas it induced significantly lower proteinuria in female rats, and cas tration significantly reduced proteinuria of male rats to an extent eq ual to the levels seen in female rats. Control male rats had significa ntly lower serum albumin levels and a significantly greater impairment of renal function (blood urea nitrogen and creatinine levels) than th e female rats or the castrated male rats at 20 weeks. The glomeruloscl erosis index was significantly higher in control male rats than in fem ale rats, and castration attenuated glomerular injury of male rats to an extent close to the levels seen in female rats, though there was a significant difference in the glomerulosclerosis index between female rats and castrated male rats, The three groups did not differ in blood pressure and plasma somatomedin C and serum growth hormone levels, wh ereas the plasma testosterone levels were decreased to undetectable in female and castrated male rats, resulting in a reduction of sex-relat ed low molecular weight protein in urine. These observations suggest t hat sex hormones such as testosterone and estrogen and/or sex-related low molecular weight protein regulated by testosterone and estrogen ma y play a contributory role in sex differences in the progression of gl omerulosclerosis in ADR-treated rats.