Raloxifene- and estradiol-mediated effects on uterus, bone and B lymphocytes in mice.
Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It is selective by having estrogen-agonistic effects on bone, vessels and blood lipids while it is antagonistic on mammary and uterine tissue. Our aim was to study the agonistic and antagonistic properties of the raloxifene analogue LY117018 (LY) on uterus, bone, B lymphopoiesis and B cell function. Oophorectomized and sham-operated animals were treated with s.c. injections of equipotent anti-osteoporotic doses of 17beta-estradiol (E2) (0.1 mg/kg) or LY (3 mg/kg) or vehicle as controls. Effects on bone mineral density (BMD) were studied using peripheral quantitative computed tomography, uterine weight was examined, B lymphopoiesis was examined using flow cytometry and B cell function in bone marrow and spleen was studied by the use of an ELISPOT assay. E2 and LY had similar effects on BMD and bone marrow B lymphopoiesis, while LY had a clear antagonistic effect on endogenous estrogen in uterine tissue and no stimulating effect on the frequency of Ig-producing B cells in sham-operated animals. Our results are discussed in the context of estrogen receptor biology, relations between the immune system and bone metabolism and also with respect to the estrogen-mediated effects on rheumatic diseases.
Erlandsson
M C
MC
Department of Rheumatology and Inflammation Research, University of Göteborg, Sweden. malin.erlandsson@rheuma.gu.se
Jonsson
C A
CA
Lindberg
M K
MK
Ohlsson
C
C
Carlsten
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D038041:Lymphopoiesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011759:Pyrrolidines / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed; D014599:Uterus / Q000187:drug effects*
D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D004958:Estradiol; C025430:LY 117018; D007334:Insulin-Like Growth Factor I