PROBLEM: Estrogen induces atrophy in the thymus by an unknown mechanism. Si
nce 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 Wester
n 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(+) thymo
cytes. Estrogen treatment decreases thymus size and increase FasL expressio
CONCLUSION: CD4(+)CD8(+) thymocytes and thymic stroma cells express ER alph
a and ERP. In vivo and in vitro we showed that estrogen treatment increases
FasL expression while decreasing thymus cell number. These findings suppor
t the hypothesis that estrogen-induced thymic atrophy occurs as a result of
apoptosis and is mediated by estrogen-induced FasL expression.