Comparative effects of estrogen and raloxifene on B lymphopoiesis and bone loss induced by sex steroid deficiency in mice.
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 17beta-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 (microCT) 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.
Onoe
Y
Y
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Miyaura
C
C
Ito
M
M
Ohta
H
H
Nozawa
S
S
Suda
T
T
D000728:Androgens / Q000172:deficiency*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology*; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D018655:Lymphocyte Count / Q000187:drug effects*; D008297:Male; D051379:Mice; D009919:Orchiectomy / Q000009:adverse effects; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000503:physiopathology; D010052:Ovariectomy / Q000009:adverse effects; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D014599:Uterus / Q000473:pathology
D000728:Androgens; D004967:Estrogens; D020849:Raloxifene Hydrochloride; D004958:Estradiol