In a variety of renal diseases, males progress at a more rapid rate and have a more fulminant course then females. This gender difference may be related to the direct effects of sex hormones on the cells of the kidney. To evaluate this hypothesis, we studied the effects of estrogens and testosterone on mesangial cell proliferation and collagen synthesis. At 48 hours, estradiol at 10 nM and 100 nM had a modest proliferative effect on cultured mesangial cells, as measured by 3H thymidine incorporation into DNA and direct cell counting. This estradiol effect was fully reversed by Tamoxifen (1 μM). Estradiol had no effect on cellular proliferation at 1 μM concentrations, but suppressed proliferation at 10 μM doses. Testosterone had a modest but statistically insignificant effect on proliferation at 10 nM and 100 nM concentrations but no effect at 1 μM or 10 μM. Neither estradiol nor testosterone at 10 μM affected total cellular protein accumulation. Estradiol at 1 μM and 10 μM, markedly suppressed total collagen synthesis as measured by 3H proline incorporation, and specifically suppressed the synthesis of collagen types I and IV, as measured by immunoprecipitation and gel electrophoresis. Testosterone did not affect collagen synthesis. Estradiol also reduced the steady state message for the α2 chain of type I collagen, while testosterone had no effect. Neither estradiol nor testosterone affected the steady state message for TGFβ or EGF. The direct effects of estradiol on mesangial cell collagen generation may help explain the slower development of glomerulosclerosis in women and therefore the 'protective' effect of female gender on the progression of renal disease.
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