Comparative Effects of Estrogen and Raloxifene on B Lymphopoiesis and Bone Loss Induced by Sex Steroid Deficiency in Mice

Authors

  • Yoshiko Onoe,

    1. Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    2. Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
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  • Chisato Miyaura,

    1. Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    2. Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
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  • Masako Ito,

    1. Department of Radiology, School of Medicine, Nagasaki University, Nagasaki, Japan
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  • Hiroaki Ohta,

    1. Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
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  • Shiro Nozawa,

    1. Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
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  • Tatsuo Suda

    Corresponding author
    1. Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    • Department of Biochemistry School of Dentistry Showa University 1–5–8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan
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Abstract

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss because of stimulated bone resorption. We have reported that OVX selectively stimulates B lymphopoiesis in mouse bone marrow, which is somehow related to bone resorption. Estrogen prevents both the increased B lymphopoiesis and the bone resorption caused by estrogen deficiency. Raloxifene also has a potent estrogenic activity for bone with minimal estrogenic activity for the uterus. To examine the effects of raloxifene on B lymphopoiesis and bone resorption, OVX mice were given either estrogen or raloxifene subcutaneously for 2–4 weeks using a miniosmotic pump. Reduced uterine weight in OVX mice was restored completely by 17β-estradiol (E2). Some 300-fold higher doses of raloxifene increased uterine weight of OVX mice, but only slightly. The number of B220- positive pre-B cells was increased markedly in bone marrow after OVX. The increased B lymphopoiesis was prevented not only by E2 but by raloxifene. In OVX mice, the trabecular bone volume (BV) of the femoral distal metaphysis was reduced markedly, when measured by microcomputed tomography (μCT) scanning and dual-energy X-ray absorptiometry. Both E2 and raloxifene similarly restored it. Like estrogen deficiency, androgen deficiency induced by orchidectomy (ORX) also resulted in a marked bone loss and increased B lymphopoiesis. Both E2 and raloxifene prevented the changes in ORX mice. These results indicate that both estrogen deficiency and androgen deficiency similarly stimulate B lymphopoiesis in mouse bone marrow, which accompany bone loss. Raloxifene exhibits estrogenic actions in bone and bone marrow to prevent bone loss and regulate B lymphopoiesis without inducing estrogenic action in the uterus.

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