THE OVARIES ATTENUATE THE AGGRAVATING EFFECT OF TESTOSTERONE ON GLOMERULAR INJURY IN ADRIAMYCIN-INDUCED NEPHROPATHY OF FEMALE RATS

To clarify whether the ovaries have a potential to attenuate the aggra vating effect of testosterone (T) on glomerular injury, we investigate d the effect of T in female rats with or without ovaries, using Adriam ycin (ADR)-induced nephropathy in female Sprague-Dawley rats. Group 1 consisted of female control rats, group 2 received T, groups 3 and 4 w ere subjected to ovariectomy (OVX) at 5 weeks of age, and group 4 rece ived further T treatment. Group 5 consisted of male control rats. T wa s injected subcutaneously every 4 weeks from 5 weeks of age through th e end of the experiment. ADR 2 mg/kg was administered intravenously to all rats twice, at 8 weeks of age and 20 days later. Body weight, blo od pressure, urinary protein and serum constituents were investigated every 4 weeks from 4 through 24 weeks after the second ADR injection. Each group was studied morphologically 24 weeks after the second ADR i njection. Treatment with T or with OVX and T significantly increased t he urinary protein excretion. OVX had no significant effect on the uri nary protein excretion. Treatment with either T or OVX did not induce any significant effects on the renal function with regard to blood ure a nitrogen (BUN), serum creatinine (Cr) and Cr clearance (Ccr) levels, but a combined treatment with OVX and T significantly lowered the ser um albumin levels, increased the levels of BUN and Cr and lowered the Ccr values. The glomerulosclerosis index was significantly and markedl y higher in control male rats than in control females. Treatment with T resulted in a slight but significant increase in glomerular injury t o levels similar to those seen in ovariectomized rats. Combined treatm ent with OVX and T significantly aggravated glomerular injury in a som ewhat accelerated manner, associated with a significant increase in gl omerular tuft volume. Our results suggested that the ovaries could not completely suppress glomerular injury worsened by T administered at s erum levels similar to those of male rats, but they had a potential to attenuate glomerular injury induced by T, and the protective effect o f the ovaries on glomerular injury may be related to their attenuating effect on glomerular growth.