Comparative effects of estrogen and raloxifene on B lymphopoiesis and bone loss induced by sex steroid deficiency in mice
Comparative effects of estrogen and raloxifene on B lymphopoiesis and bone loss induced by sex steroid deficiency in mice
复制标题
DOI：
10.1359/jbmr.2000.15.3.541
复制
发表时间：
2000-03-01
影响因子：
6.2
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Onoe, Y;Miyaura, C;Suda, T
卵巢切除术（ovariectomy，OVX）引起的雌激素缺乏可引起明显的骨吸收，从而引起骨丢失。我们曾报道OVX选择性地刺激小鼠骨髓B淋巴细胞生成，这与骨吸收有关。雌激素既可防止B淋巴细胞生成增加，又可防止雌激素缺乏引起的骨吸收。雷洛昔芬对骨也具有有效的雌激素活性，对子宫具有最小的雌激素活性。为了检查雷洛昔芬对B淋巴细胞生成和骨吸收的作用，使用微量渗透泵皮下给予OVX小鼠雌激素或雷洛昔芬2-4周。17 β-雌二醇（E-2）完全恢复了OVX小鼠子宫重量减轻的情况，高剂量约300倍的雷洛昔芬增加了OVX小鼠的子宫重量，但幅度很小，OVX后骨髓中B220阳性前B细胞数量显着增加，E-2和雷洛昔芬都可以阻止B淋巴细胞生成的增加，在OVX小鼠中，通过微型计算机断层扫描（mu CT）扫描和双能X射线吸收测定法测量，股骨远端干骺端的骨小梁体积（BV）明显减少，E-2和雷洛昔芬都类似地恢复了它。与雌激素缺乏一样，睾丸切除术（ORX）引起的雄激素缺乏也导致明显的骨质丢失和B淋巴细胞生成增加，E-2和雷洛昔芬都阻止了ORX小鼠的变化。这些结果表明，雌激素缺乏和雄激素缺乏同样刺激小鼠骨髓中的B淋巴细胞生成，这伴随着骨丢失。雷洛昔芬在骨和骨髓中表现出雌激素作用，可防止骨质流失并调节B淋巴细胞生成，而不会诱导子宫中的雌激素作用。
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 17 beta-estradiol (E-2), 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 E-2 but by raloxifene, In OVX mice, the trabecular bone volume (BV) of the femoral distal metaphysis was reduced markedly, when measured by microcomputed tomography (mu CT) scanning and dual-energy X-ray absorptiometry, Both E-2 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 E-2 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.