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.

Nyckelord

Animals

B-Lymphocytes

drug effects

Bone and Bones

drug effects

Estradiol

pharmacology

Female

Flow Cytometry

Immunoenzyme Techniques

methods

Insulin-Like Growth Factor I

drug effects

Lymphopoiesis

drug effects

Mice

Mice

Inbred C57BL

Pyrrolidines

pharmacology

Selective Estrogen Receptor Modulators

pharmacology

Spleen

drug effects

Thiophenes

pharmacology

Tomography

X-Ray Computed

Uterus

drug effects

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