ATTENUATING EFFECT OF CASTRATION OR ESTROGEN ADMINISTRATION ON GLOMERULAR INJURY IN ADRIAMYCIN-INDUCED NEPHROPATHY OF RATS

To clarify the role of sex-related factors in the development of focal segmental glomerulosclerosis (FSGS) we investigated the effect of cas tration or oestrogen administration in adriamycin (ADR)-induced nephro pathy of Sprague-Dawley rats. At 5 weeks of age, group 1 (control grou p) and group 3 were sham-operated and group 2 was castrated. Adriamyci n 2 mg/kg was administered intravenously to all rats at 8 weeks of age twice at a 20-day interval. Group 3 was administered 0.2 mg oestrogen subcutaneously once a month. Bodyweight (BW) and urinary protein were measured every 4 weeks from 15 to 23 weeks of age. Blood pressure wee ks of age. Adriamycin induced massive proteinuria in group 1, whereas castration or oestrogen significantly attenuated proteinuria, accompan ied by a significant reduction of urinary sex-related low molecular we ight (LMW) protein. The glomerulosclerosis index was significantly hig her in the control group than in the castrated group or oestrogen-trea ted group. Attenuation in glomerular injury was more associated with r eduction of urinary sex-related LMW protein than the reduction of seru m testosterone. These observations suggest that sex-related factors, s uch as a sex-related LMW protein, influenced by castration or oestroge n administration may play a contributory role in the development of gl omerulosclerosis in ADR-induced nephropathy.