Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model
Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model
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DOI：
10.3181/00379727-217-44243
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发表时间：
1998-03-01
影响因子：
--
通讯作者：
Garner, SC
中科院分区：
文献类型：
--
作者：
Anderson, JJB;Ambrose, WW;Garner, SC
采用去卵巢(OVX)哺乳大鼠模型，研究了植物雌激素染料木素在14天内对骨骼的影响。低钙饮食的OVX哺乳大鼠在哺乳的前两周会损失略高于50%的骨矿物质，我们已经证明雌激素治疗可以显著减少股骨质量的损失(鞭毛重量)。OVX后，大鼠被分配到治疗组或对照组(安慰剂和雌激素替代阳性对照组)。试验组每天通过饲料摄入三种富含染料木素的制剂中的一种，持续两周，之后幼崽开始对固体饲料产生兴趣。阳性对照组在饲料中加入结合雌激素。染料木素剂量分别为：低剂量(0.5 mg/d)、中剂量(1.6 mg/d)和高剂量(5.0 mg/d)。测量内容包括股骨灰重、胫骨近端扫描电子显微镜(SEM)和子宫重量。扫描电子显微镜结果如下：(1)在保留松质骨组织方面，低剂量金雀异黄素的作用与雌激素大致相同，表现在胫骨平台下半横断处的骨小梁数量和密度上，但高剂量金雀异黄素的作用较差；(2)与未经处理的对照组大鼠相比，低剂量金雀异黄素治疗的大鼠骨内膜表面更加粗糙，孔洞更小。与对照组相比，低剂量组大鼠股骨平均灰重最高(P<；0.05)，且高于中、高剂量金雀异黄素组。扫描电子显微镜观察到股骨的平均灰重与金雀异黄素对胫骨的影响一致。综上所述，在这个去势大鼠模型中发现了对染料木素制剂的双相反应。对结果的解释表明，在低剂量时，金雀异黄素似乎是雌激素受体基因座的激动剂，而在高剂量时，金雀异黄素的效果较差，甚至可能对骨细胞产生不利影响。金雀异黄素的双相效应(即倒U效应)的这些发现与最近文献中关于分离的骨细胞和生殖组织的其他报道一致。总而言之，大豆食品中较低剂量的染料木素对骨组织的作用与雌激素相似，对骨组织有有益的影响，但在人类饮食中不太可能摄入的高剂量染料木素，这种大豆衍生品可能会对骨细胞功能产生潜在的不利影响，从而对骨组织产生不利影响。
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 lash 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.