Testosterone does not eliminate the attenuating effect of estrogen on progressive glomerular injury in estrogen-treated hypercholesterolemic male Imai rats

Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially males. Estrogen attenuates the progressive glomerular injury in these male rats. To clarify whether this attenuating effect of estrogen depends on a reduction of testosterone and/or a reduction of the sex-related factors, we investigated whether testosterone administration eliminates the attenuating effect of estrogen on the development of glomerular injury in estrogen-treated male Imai rats. Estrogen significantly reduced sex-related low molecular weight protein excretion to undetectable levels; and treatment with estrogen and testosterone failed to increase these levels. Unexpectedly, treatment with estrogen and testosterone attenuated glomerular injury more than treatment with estrogen only. Estrogen significantly increased both levels of estrogen and growth hormone (GH), whereas it suppressed testosterone levels. Testosterone administration resulted in an increase in serum testosterone levels of about fivefold above the control levels, but reduced the elevated serum GH to the levels of the controls. These results suggest that estrogen appears to play a protective role by itself or in association with sex-related factors, independent of the levels of serum testosterone, and that testosterone does not exert its effect on augmenting glomerular injury and rather may act to attenuate glomerular injury associated with a reduction of GH levels.