| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Takako Tokyo Women's Medical University, Dept of OB & GY, Assistant, 医学部, 助手 (80339019)
IWABUCHI Michiko Tokyo Women's Medical University, Dept of OB & GY, Assistant, 医学部, 助手 (00322488)
OKANO Hiroya Tokyo Women's Medical University, Dept of OB & GY, Assistant, 医学部, 准講師 (20339021)
YOSHIKATA Remi Tokyo Women's Medical University, Dept of OB & GY Assistant, 医学部, 助手 (00318023)
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| Research Abstract |
Estrogen deficiency causes markedly bone loss, and can be prevent by estrogen replacement therapy, Raloxifene, which is recognized as one of Selective Estrogen Receptor Modulator, have reported that reduced bone loss without estrogenic in uterus. GnRH agonist (GnRHa) is useful for estrogen dependent disease since rhythmical secretion of gonadotropin is decreased, but long-term treatment of GnRHa is led to bone loss by increasing bone resorption. In the present study, we examined that to cause secondary bone loss in mice by GnRHa, and the effect of raloxifene to this.
8w female ddy mice were injected with GnRHa (5 mg/kg) every 4 weeks for 4 weeks to 12 weeks. Some of the GnRHa treated mice combined Raloxifene (1 mg/kg/day) or 17β-Estradiol (1 microg/kg/day) subcutaneously using an Alzet pump. Ovariectmized (OVX) mice were prepared and treated with Raloxifene or 17β-estradiol for control.
In OVX mice, uterine weight were markedly decreased and uteri were atrophied, but in GnRHa treated mice, uterine weight were slightly reduced. However, serum FSH level were remarkably high as compared with vehicle mice, we concluded that the atrophic level of uterine is maximum which may be caused by GnRHa. The femoral bone mineral density (BMD) in GnRHa mice were significantly reduced, and these were similar to OVX mice. In OVX mice, 17β-Estradiol recovered both uterine weight and bone loss, but Raloxifene only prevent bone loss. Similarly, in GnRHa treated mice, Raloxifene recovered bone loss, but uterine weight did not have effect. Serum OPG level were higher in GnRHa treated mice than in vehicle mice, furthermore Raloxifene decreased these till lower than vehicle level.
In conclusion, these results indicate that treatment of GnRHa caused bone loss in female mice, and Raloxifene can be prevent bone loss without estrogenic action in uterus. It is possible that Raloxifene is very useful for add-back therapy agonist GnRHa.
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