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 aggravating effect of testosterone (T) on glomerular injury, we investigated the effect of T in female rats with or without ovaries, using Adriamycin (ADR)-induced nephropathy in female Sprague-Dawley rats. Group 1 consisted of female control rats, group 2 received T, groups 3 and 4 were subjected to ovariectomy (OVX) at 5 weeks of age, and group 4 received further T treatment. Group 5 consisted of male control rats. T was injected subcutaneously every 4 weeks from 5 weeks of age through the 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, blood 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 injection. Treatment with T or with OVX and T significantly increased the urinary protein excretion. OVX had no significant effect on the urinary protein excretion. Treatment with either T or OVX did not induce any significant effects on the renal function with regard to blood urea nitrogen (BUN), serum creatinine (Cr) and Cr clearance (Ccr) levels, but a combined treatment with OVX and T significantly lowered the serum albumin levels, increased the levels of BUN and Cr and lowered the Ccr values. The glomerulosclerosis index was significantly and markedly higher in control male rats than in control females. Treatment with T resulted in a slight but significant increase in glomerular injury to levels similar to those seen in ovariectomized rats. Combined treatment with OVX and T significantly aggravated glomerular injury in a somewhat accelerated manner, associated with a significant increase in glomerular tuft volume. Our results suggested that the ovaries could not completely suppress glomerular injury worsened by T administered at serum levels similar to those of male rats, but they had a potential to attenuate glomerular injury induced by T, and the protective effect of the ovaries on glomerular injury may be related to their attenuating effect on glomerular growth.