The role of the Fas/Fas ligand system in estrogen-induced thymic alteration

PROBLEM: Estrogen induces atrophy in the thymus by an unknown mechanism. Since the Fas/FasL system is one of the main pathways in T cell apoptosis, we tested the hypothesis that estrogen-induced thymic atrophy is mediated by the Fas/FasL system. METHODS OF STUDY: In vivo experiments were done using ovariectomized female rats treated with estrogen or saline. In vitro experiments were performed using isolated thymocytes. Estrogen receptor (ER) alpha and beta expression was characterized using flow cytometry, RT-PCR and immunofluorescence. Fas and FasL mRNA and protein expression was evaluated using RT-PCR and Western blot analysis respectively. RESULTS: ER alpha and ER beta are present in thymocytes and stromal cells. ER expression is mainly localized in the Double Positive CD4(+)CD8(+) thymocytes. Estrogen treatment decreases thymus size and increase FasL expression. CONCLUSION: CD4(+)CD8(+) thymocytes and thymic stroma cells express ER alpha and ERP. In vivo and in vitro we showed that estrogen treatment increases FasL expression while decreasing thymus cell number. These findings support the hypothesis that estrogen-induced thymic atrophy occurs as a result of apoptosis and is mediated by estrogen-induced FasL expression.