17 beta-Estradiol and steady-state concentrations of H_2O_2: antiapoptotic effect in endometrial cells from patients with endometriosis

摘要

Increased levels of hydrogen peroxide (H_2O_2) can initiate protective responses to limit or repair oxidative damage. However, H_2O_2 signals also fine-tune responses to growth factors and cytokines controlling cell division, differentiation, and proliferation. Because 17 beta-estradiol (E_2) also plays important roles in these processes, and is considered a major risk factor in the development and progression of endometriosis, this study evaluated whether E_2 has an antiapoptotic effect on oxidative stress in endometrial cells in combination with steady-state H_2O_2 levels ([H_2O_2]ss). Endometrial stromal cells were prepared from the eutopic endometrium of 18 women with and without endometriosis to produce primary cells. These cells were stimulated with E2 for 20 h, exposed to [H_2O_2]ss, and examined for cell viability, proliferation, and apoptosis. The endometrial cells from women with endometriosis maintained the steady state for 120 min at high H_2O_2 concentrations. When they were pretreated with E2 and exposed to [H_2O_2]ss, a decrease in apoptosis level was observed compared to the control cells (p<0.01). The endometrial cells from patients with endometriosis subjected to both E2 and [H2O2]ss showed increased ERK phosphorylation. These findings suggested that H2O2 is a signaling molecule that downregulates apoptosis in endometrial cells, supporting the fact that endometriosis, albeit a benign disease, shares some features with cancer such as decreased catalase levels. These results link the E_2 effects on [H_2O_2]ss to resistance to apoptosis and progression of endometriosis.