Effects of sex hormones on mesangial cell proliferation and collagen synthesis

In a variety of renal diseases, males progress at a more rapid rate and have a more fulminant course than 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 H-3 thymidine incorporation into DNA and direct cell counting. This estradiol effect was fully reversed by Tamoxifen (1 mu M), Estradiol had no effect on cellular proliferation at 1 mu M concentrations, but suppressed proliferation at 10 mu M doses. Testosterone had a modest but statistically insignificant effect on proliferation at 10 nM and 100 nM concentrations but no effect at 1 mu M or 10 mu M. Neither estradiol nor testosterone at 10 mu M affected total cellular protein accumulation. Estradiol at 1 mu M and 10 mu M, markedly suppressed total collagen synthesis as measured by H-3 proline incorporation, and specifically suppressed the synthesis of collagen types I and TV, as measured by immunoprecipitation and gel electrophoresis. Testosterone did not affect collagen synthesis. Estradiol also reduced the steady state message for the alpha 2 chain of type I collagen, while testosterone had no effect. Neither estradiol nor testosterone affected the steady state message for TGF beta or EGF. The direct effects of estradiol on mesangial cell collagen generation map help explain the slower development of glomerulosclerosis in women and therefore the ''protective'' effect of female gender on the progression of renal disease.