Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ERα expression and uterine wet weight in ovariectomized rats

• Published in: Journal of bone and mineral metabolism 2011-07, Vol.29 (4), p.396-403
• Main Authors: Li, Xu, Song, Quan-Sheng, Wang, Jing-Ying, Leng, Hui-jie, Chen, Zhong-Qiang, Liu, Zhong-Jun, Dang, Geng-Ting, Song, Chun-Li
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Animals; Biological and medical sciences; Biomechanical Phenomena - drug effects; Blotting, Western; Body Weight - drug effects; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - pathology; Bone and Bones - physiopathology; Bone Density - drug effects; Bone Resorption - pathology; Bone Resorption - physiopathology; Diseases of the osteoarticular system; Estrogen Receptor alpha - metabolism; Female; Immunohistochemistry; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - pathology; Lumbar Vertebrae - physiopathology; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Original Article; Orthopedics; Osteoporosis. Osteomalacia. Paget disease; Ovariectomy; Rats; Rats, Sprague-Dawley; Simvastatin - pharmacology; Uterus - drug effects; Uterus - metabolism; Uterus - pathology
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-010-0231-y

We previously reported that simvastatin induces estrogen receptor-alpha (ERα) in murine bone marrow stromal cells in vitro. In this study, we investigated the effect of simvastatin on ERα expression in bone and uterus in ovariectomized (OVX) rats and evaluated bone mass, bone strength, and uterine wet weight. Three-month-old Sprague–Dawley female rats received OVX or sham operation. Six weeks later, the rats were treated orally with simvastatin (5 or 10 mg/kg/day), or intraperitoneally with 17-β-estradiol (E 2 ) or a combination of simvastatin and E 2 for 6 weeks. Uterine wet weight, bone mineral density (BMD) of lumbar vertebrae, biomechanics of lumbar vertebrae, and induction of ERα expression in the bone and uterus were analyzed. The 6-week simvastatin treatment improved lumbar vertebral BMD and boosted biomechanical performance of the vertebral body compared to the OVX control, suggesting that simvastatin can treat osteoporosis caused by estrogen deficiency. More interestingly, simvastatin could increase ERα expression and synergy with estradiol in bone while antagonizing estradiol in the uterus, along with uterus atrophy and uterine wet weight decreases. In conclusion, these data suggest that simvastatin exert opposing modulatory effects on ERα expression on bone and uterus in ovariectomized rats, inducing ERα expression and synergy with estrogen to perform anabolic effects on the bones while decreasing E2 efficacy and uterine wet weight. This finding may be helpful to explain the mechanism of statin treatment in osteoporosis caused by estrogen deficiency.