Is high-dose estrogen-induced osteogenesis in the mouse mediated by an estrogen receptor?
Is high-dose estrogen-induced osteogenesis in the mouse mediated by an estrogen receptor?
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DOI：
10.1016/s8756-3282(00)00289-1
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发表时间：
2000-07-01
期刊：
影响因子：
4.1
通讯作者：
Tobias, JH
中科院分区：
文献类型：
--
作者：
Samuels, A;Perry, MJ;Tobias, JH
尽管已知雌激素会诱导雌性小鼠长骨中的新骨形成，但这种反应仅在施用高剂量后才会发生，这表明它可能不是由传统雌激素受体介导的。为了进一步解决这个问题，我们首先通过比较17β-雌二醇（E（2））刺激完整雌性小鼠胫骨近端干骺端松质骨形成的效力与相对不活跃的立体异构体17α-雌二醇（αE（2））来检查该反应的立体特异性。我们发现，通过组织形态计量学评估，E(2) 明显比 α E(2) 更有效，为了为雌激素受体介导的过程提供进一步的证据，我们检查了雌激素受体拮抗剂 ICI 182,780 (ICI) 是否可以抑制 E(2) 诱导的完整雌性小鼠成骨，虽然 ICI 本身在单独给药时对近端胫骨干骺端的组织形态计量指数没有影响，但它显着抑制对 E(2) 的成骨反应。最后，我们检查了完整小鼠胫骨近端干骺端E(2)诱导的成骨的剂量依赖性。我们发现，E(2) 在较宽的剂量范围（即每天 1-4000 μg/kg）内以剂量依赖性方式刺激松质骨形成，在每天 4 μg/kg 及以上的剂量下观察到显着增加。我们的结果提出了一种可能性，即雌激素诱导的小鼠成骨代表了雌激素受体介导的反应，该反应不仅仅局限于超生理雌激素水平。 (Bone 27:41-46; 2000) (C) 2000 Elsevier Science Inc. 保留所有权利。
Although estrogen is known to induce new bone formation in the long bones of female mice, this response is only thought to occur following administration of high doses, suggesting that it may not be mediated by a conventional estrogen receptor. To address this question further, we first examined the stereospecificity of this response by comparing the potency of 17 beta-estradiol (E(2)) in stimulating cancellous bone formation at the proximal tibial metaphysis of intact female mice with that of the relatively inactive stereoisomer, 17 alpha-estradiol (alpha E(2)). We found that E(2) was significantly more potent than alpha E(2), as assessed by histomorphometry, To provide further evidence for an estrogen-receptor-mediated process, we examined whether E(2)-induced osteogenesis in intact female mice could be inhibited by the estrogen receptor antagonist, ICI 182,780 (ICI), Although ICI itself had no effect on histomorphometric indices of the proximal tibial metaphysis when given alone, it significantly inhibited the osteogenic response to E(2). Finally, we examined the dose dependency of E(2)-induced osteogenesis at the proximal tibial metaphysis in intact mice. We found that E(2) stimulated cancellous bone formation in a dose-dependent manner over a wide dose range (i.e., 1-4000 mu g/kg per day), with significant increases observed at doses of 4 mu g/kg per day and beyond. Our results raise the possibility that estrogen-induced osteogenesis in the mouse represents an estrogen-receptor-mediated response that is not confined solely to supraphysiological estrogen levels; (Bone 27:41-46; 2000) (C) 2000 by Elsevier Science Inc. All rights reserved.