中年期過後,隨著年齡的增加,骨質會慢慢流失。尤其是停經後的婦女,因體內雌激素的減少,發生骨質疏鬆症(osteoporosis)的比率較高。雌激素補充療法(estrogen replacement therapy, ERT)對於停經後婦女之骨質疏鬆有減緩骨質流失的療效,但是許多研究指出長期服用雌激素會增加乳癌、子宮內膜癌及卵巢癌的發生。近年來發現植物中,含有多種與雌激素結構或生物功能相似的成分,如:豆科植物中之genistein、daidzein及菊科植物中之coumestrol,稱之為植物雌激素(phytoestrogen)。本研究欲探討植物雌激素是否可取代雌激素成為在骨質疏鬆的治療上更安全的藥物。 本研究以兩種不同生長階段(初生四天之幼鼠及八個月大之成鼠)之小鼠為動物模式,探討在細胞分子層面上植物雌激素與雌激素具有相同或不同的回應機制,特別是與雌激素接受體的關係,了解植物雌激素對骨母細胞的影響。培養兩種不同生長階段的小鼠之骨母細胞,給予植物雌激素及雌激素藥物,分別在1、7、14、21天利用細胞活性、鹼性磷酸?、鈣含量及即時定量反轉錄聚合?連鎖反應來探討植物雌激素對骨母細胞的影響。 結果發現,以新生鼠骨母細胞實驗模式下,daidzein不具有增加細胞活性,也就是不會使細胞增生。另一個植物雌激素coumestrol就具有使新生鼠骨母細胞增生,在10-9 M有最高的促進率。而在成鼠骨母細胞實驗模式下,植物雌激素(daidzein和coumestrol)比E2更能促進細胞活性。所以coumestrol對於新生鼠和成鼠都具有細胞增生的作用,其中又以對成鼠的效果最佳,本實驗以八個月的雌性成鼠模擬更年期的婦女,因此,coumestrol可能對於更年期婦女骨質疏鬆的治療具有正面的意義。
Postmenopausal osteoporosis is a metabolic bone disease characterized by a decrease of bone mass after menopause, which may lead to spontaneous and traumatic fractures in still-active women. In postmenopausal women, the bone loss is sufficient to cause osteoporosis. Several studies have shown that estrogen replacement therapy (ERT) contributes to maintenance of skeletal mass and can reduce the risk of fractures in postmenopausal women. But long-term ERT has been associated with increased risk of cancer in estrogen target tissues, including the mammary gland and uterus. In recent years, find some composition in plant that similar to estrogen structure or the biological function. The research wants to probe into the estrogen in plant (phytoestrogen) and can replace estrogen and become the safer medicine in the treatment of the osteoporosis. In this study, we assessed the effects of the phytoestrogen on cell proliferation, ALP activity and calcium accumulation in osteoblast from neonatal mice. Furthermore, the cells transcriptionally expressed the detectable levels of collagen type I, ALP, OPG, OPGL, estrogen receptors (ERα and ERβ) mRNAs. The results presented herein characterize the cellular effects of phytoestrogen on bone tissue. Phytoestrogen induced a increase in osteoblast proliferation, with the optimum effects at 10-9 M. We tested osteoblasts with phytoestrogen and assessed the cellular expression of osteoblast-specific genes by real-time PCR. Phytoestrogen can decrease the bone mass loss by increase bone formation, which prevents the development of osteoporosis.