| Popis: |
Estrogen (E) deficiency caused by ovariectomy (OVX) results in marked bone loss because of increased bone resorption. We have reported that OVX selectively stimulated pre-B lymphopoiesis in mouse bone marrow. Estrogen prevented both increased pre-B lymphopoiesis and bone resorption. In vitro, co-culture system with ST2, a murine stromal cell line, and murine bone marrow cells supported pre-B lymphopoiesis, and 17β-estradiol (E_2) decreased colony formation by pre-B lymphocytes. Adhesion between ST2 cells and pre-B lymphocyte cell line induced secretion of IL-6 from ST2 and stimulated bone resorption. These results suggest that increased B-lymphopoiesis due to E deficiency is involved in stimulation of bone resorption. We examined the expression of estrogen receptor β (ERβ) mRNA in bone and other tissues and found high expression of ERβ mRNA in osteoblastic cells of rat bone. The level of ERβ mRNA expression was substantially higher in cancellous bone than in cortical bone, and the level of ERβ expression was similar in male and female rats. These results suggest that ERβ plays a distinct role in the regulation of E in bone. We examined the effect of raloxifene on pre-B lymphopoiesis and bone resorption. Reduced uterine weight in OVX mice was completely restored by E. About 300-fold higher doses of raloxifene slightly increased uterine weight in OVX mice. The increased B-lymphopoiesis caused by OVX was prevented not only by E_2 but also by raloxifene. In OVX mice, the trabecular bone volume of the femoral distal metaphysis decreased markedly on dual energy X-ray absorptiometry. Both E_2 and raloxifene similarly restored this decrease in bone volume. Similar to E deficiency, androgen deficiency caused by orchidectomy (ORX) also induced marked bone loss and stimulated pre-B lymphopoiesis in bone marrow of male mice. In ORX mice, seminal vesicle weight and femoral BMD also decreased. Both E and raloxifene normalized the stimulated B-lymphopoiesis and bone resorption induced by ORX. These results show that E also regulates B-lymphopoiesis and bone resorption in male mice. In conclusion, we studied the effects of raloxifene on B-lymphopoiesis and bone mass in OVX and ORX mice to explore the relation between B-lymphopoiesis and bone resorption, both of which are regulated by sex steroids. In both female and male mice, raloxifene had estrogenic actions in bone and bone marrow, preventing bone loss and normalizing stimulated B-lymphopoiesis without appreciably affecting reproductive tissues. |
