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

Citation
G. Mor et al., The role of the Fas/Fas ligand system in estrogen-induced thymic alteration, AM J REPROD, 46(4), 2001, pp. 298-307
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
ISSN journal
1046-7408 → ACNP
Volume
46
Issue
4
Year of publication
2001
Pages
298 - 307
Database
ISI
SICI code
1046-7408(200110)46:4<298:TROTFL>2.0.ZU;2-K
Abstract
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 n. 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.