Effect of treatment with different doses of 17-beta-estradiol on insulin receptor substrate-1.

CONTEXT Ovarian hormones modulate insulin sensitivity, but their exact role remains unclear. OBJECTIVE We tried to determine whether different doses of 17-beta-estradiol cause changes in the regulation of insulin receptor substrate (IRS-1) levels, and if so, the possible implications in insulin sensitivity. DESIGN Ovariectomized rats were treated with different doses of 17-beta-estradiol at 6, 11 and 16 days. MAIN OUTCOME MEASURES Immunoprecipitation and Western blotting for IRS-1 were performed in different tissues. RESULTS We found that estradiol treatment has an influence on the amount of IRS-1 but that it acts in different ways depending on the tissue studied, on the length of treatment, and on the doses employed. CONCLUSIONS Our results suggest that low concentrations of 17-beta-estradiol could be responsible for the upregulation of insulin receptor substrate 1, increasing insulin sensitivity in muscle and adipose tissue. However, insulin receptor substrate 1 is downregulated with high concentrations of 17-beta-estradiol, thus these high hormone plasma levels could favour insulin resistance in peripheral tissues. The role of 17-beta-estradiol seems to modulate insulin receptor substrate 1 levels in insulin dependent tissues, but in a different manner in each tissue. These novel findings are important for improving knowledge about the possible risk for insulin resistance in women taking oral contraceptives or receiving hormone replacement therapy at menopause.