Anderson J J, Ambrose W W, Garner S C
Department of Nutrition, University of North Carolina, Chapel Hill 27599-7400, USA.
Proc Soc Exp Biol Med. 1998 Mar;217(3):345-50. doi: 10.3181/00379727-217-44243.
The ovariectomized (OVX), lactating rat model has been used to investigate the skeletal effects of the plant estrogen, genistein, over a 14-day period. The OVX, lactating rat on a low-calcium diet loses slightly more than 50% of its bone mineral mass during the first 2 weeks of lactation, and we have demonstrated that estrogen treatment can significantly reduce the loss of femoral mass (ash weight). Following OVX, the rats were assigned to treatment or control groups (both placebo and positive control with estrogen replacement). The treatment groups received one of three doses of a genistein-rich preparation each day via the feed for 2 weeks, after which time the pups began to have an interest in solid feed. A positive control group received conjugated estrogen in the feed. The genistein doses were: low (0.5 mg/d); intermediate (1.6 mg/d); and high (5.0 mg/d). Measurements included ash weights of the femur, scanning electron microscopy (SEM) of the proximal tibia, and uterine weights. SEM results were as follows: (1) at the low dose genistein was approximately equally effective to estrogen in the retention of cancellous bone tissue, as reflected in the number and density of trabeculae in hemisections of the tibial subepiphyseal region, but at high doses genistein was less effective; and (2) rats treated with low-dose genistein, like estradiol, had rougher endosteal surfaces and smaller pores on these surfaces than untreated control rats. Mean ash weights of the entire femur were highest in the rats treated with the low dose compared to control rats (P < 0.05), and they were higher than ash weights of rats administered the intermediate or high doses of genistein. The mean ash weights of the femurs were consistent with the genistein effects on the tibias observed by SEM. In summary, a biphasic response to the genistein preparation was found in this OVX rat model. Interpretation of the results suggests that, at the low dose, genistein appears to be an agonist at the estrogen receptor locus, whereas at higher doses the genistein is less effective and may even have adverse effects on bone cells. These findings of a biphasic effect of genistein (i.e., an inverted U effect) are consistent with those of other recent reports in the literature on isolated bone cells and on reproductive tissues. In summary, lower doses of genistein from soy foods would be expected to act similarly to estrogens with a beneficial effect on bone tissue, but at high doses that are unlikely to be consumed in human diets, this soy derivative may have potentially adverse effects on bone cell functions and thereby on bone tissue.
已使用去卵巢（OVX）的哺乳期大鼠模型，在14天的时间里研究植物雌激素染料木黄酮对骨骼的影响。低钙饮食的OVX哺乳期大鼠在哺乳期的前2周内，其骨矿物质质量损失略超过50%，并且我们已经证明雌激素治疗可显著减少股骨质量（灰重）的损失。OVX后，将大鼠分为治疗组或对照组（安慰剂组和雌激素替代阳性对照组）。治疗组每天通过饲料接受三种剂量之一的富含染料木黄酮的制剂，持续2周，之后幼崽开始对固体饲料产生兴趣。阳性对照组在饲料中接受共轭雌激素。染料木黄酮的剂量分别为：低剂量（0.5毫克/天）；中剂量（1.6毫克/天）；高剂量（5.0毫克/天）。测量指标包括股骨的灰重、胫骨近端的扫描电子显微镜（SEM）检查以及子宫重量。SEM结果如下：（1）在低剂量时，染料木黄酮在保留松质骨组织方面与雌激素的效果大致相同，这在胫骨骨骺下区域半切片中的小梁数量和密度上有所体现，但在高剂量时染料木黄酮的效果较差；（2）与未治疗的对照大鼠相比，用低剂量染料木黄酮治疗的大鼠，其骨内膜表面更粗糙，这些表面的孔隙更小，与雌二醇治疗的大鼠情况类似。与对照大鼠相比，低剂量治疗的大鼠整个股骨的平均灰重最高（P < 0.05），且高于给予中剂量或高剂量染料木黄酮的大鼠的灰重。股骨的平均灰重与通过SEM观察到的染料木黄酮对胫骨的影响一致。总之，在这个OVX大鼠模型中发现了对染料木黄酮制剂的双相反应。结果解释表明，在低剂量时，染料木黄酮似乎是雌激素受体位点的激动剂，而在高剂量时，染料木黄酮效果较差，甚至可能对骨细胞产生不利影响。染料木黄酮双相作用（即倒U形效应）的这些发现与文献中最近关于分离的骨细胞和生殖组织的其他报道一致。总之，预计来自大豆食品的较低剂量染料木黄酮的作用类似于雌激素，对骨组织有有益影响，但在人类饮食中不太可能摄入的高剂量下，这种大豆衍生物可能对骨细胞功能进而对骨组织产生潜在的不利影响。
