title: Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent.
abstract: Estrogen has extensive effects on the immune system. The aim of the present experiments was to compare the effects of 17beta-estradiol (E2) and 4-estren-3alpha,17beta-diol (estren) on T lymphopoiesis and T cell-dependent inflammation. In order to investigate the role of estrogen receptors (ER) in the effects of E2 and estren on the immune system, ER knock-out mice lacking both ERalpha and ERbeta (DERKO) were used. T lymphopoiesis and T cell-dependent inflammation were studied by investigating thymus cellularity, the delayed-type hypersensitivity (DTH) reaction, CD4(+) T cells in spleen and serum levels of interleukin (IL)-6. As expected, the presence of ERs was mandatory for all the effects of E2. In contrast, treatment with estren reduced thymus cellularity in ER knock-out mice, indicating an effect through ER-independent pathways. Interestingly, estren suppressed only DTH, the frequency of CD4(+) T cells in spleen and serum levels of IL-6 in wild-type (WT) mice, but not in mice lacking ERs. Thus, our study is the first to show that estren inhibits T lymphopoiesis via ER-independent pathways, whereas its suppressive effects on inflammation are ER-dependent.
authors.affiliation: Department of Rheumatology and Inflammation Research at the Sahlgrenska Academy, Göteborg, Sweden. ulrika.islander@rheuma.gu.se
authors.forename: U
authors.initials: U
authors.lastname: Islander
authors.forename: M C
authors.initials: MC
authors.lastname: Erlandsson
authors.forename: T
authors.initials: T
authors.lastname: Chavoshi
authors.forename: C
authors.initials: C
authors.lastname: Jochems
authors.forename: S
authors.initials: S
authors.lastname: Movérare
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: J-A
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: H
authors.initials: H
authors.lastname: Carlsten
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003864:Depression, Chemical; D004958:Estradiol / Q000097:blood / Q000276:immunology; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D038041:Lymphopoiesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011960:Receptors, Estrogen / Q000276:immunology*
chemical_list: C468666:4-estren-3,17-diol; D004963:Estrenes; D015850:Interleukin-6; D011960:Receptors, Estrogen; D004958:Estradiol