Somjen Dalia, Katzburg Sara, Kohen Fortune, Gayer Batya, Sharon Orly, Hendel David, Posner Gary H, Kaye Alvin M
Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center, 6 Weizman St., Tel-Aviv 64239, Israel.
J Steroid Biochem Mol Biol. 2006 Feb;98(2-3):139-46. doi: 10.1016/j.jsbmb.2005.08.016. Epub 2006 Jan 10.
We have reported previously, that female-derived bone cells responded to 17beta-estradiol (E(2)) and raloxifene (Ral), and male-derived cells responded only to dihydrotestosterone (DHT) when the stimulation of creatine kinase specific activity (CK), which is a marker for hormone responsiveness, was measured. We also found that pre-treatment with the less-calcemic analog of Vitamin D, JK 1624 F(2)-2 (JKF), upregulated the response of CK to E(2) and Ral. In this study, we analyzed the response of human bone cells from pre- and post-menopausal females and males, to phytoestrogens. Bone cells derived from pre-menopausal women showed greater stimulation of CK than cells from post-menopausal women, after treatment with E(2) (30 nM), daidzein (D, 3000 nM), genistein (G, 3000 nM) and Ral (3000 nM); whereas the responses to biochainin A (BA 3000 nM), quecertin (Qu 3000 nM) or the carboxy derivative of G (cG 300 nM) were not age-dependent. Male-derived cells did not respond to phytoestrogens. When cells derived from female bones at both age groups were pre-treated with JKF, by daily addition of 1nM, for 3 days, there was an upregulation of the response to E(2), Ral, G and D but not to BA or Qu. Nuclear binding of (3)[H] E(2) was characteristic of the different phytoestrogens, with increase of the specific binding after pre-treatment with JKF. In contrast, the membranal binding of E(2)-Ov-Eu, which was specific for the estrogenic compounds except Ral, was inhibited by pre-treatment with JKF except for ICI 161480 (ICI). Male bone cells did not bind E(2)-Ov-Eu but bound T-BSA-Eu; this binding was abolished by pre-treatment with JKF. Pre-treatment with JKF increased mRNA for ERalpha and decreased mRNA for ERbeta in bone cells from both age groups of females and from males, all of which expressed both ERs, with a ratio of ERalpha to ERbeta of 121:1 in pre- and 78:1 in post-menopausal and 105:1 in male bone cells. This study raises the possibility of combined Vitamin D analog and phytoestrogen for hormonal replacement therapy to prevent post-menopausal osteoporosis, which is a subject of ongoing research in animal models.
我们之前曾报道，当测量作为激素反应性标志物的肌酸激酶比活性（CK）的刺激情况时，源自女性的骨细胞对17β - 雌二醇（E₂）和雷洛昔芬（Ral）有反应，而源自男性的细胞仅对二氢睾酮（DHT）有反应。我们还发现，用维生素D的低钙类似物JK 1624 F₂ - 2（JKF）预处理可上调CK对E₂和Ral的反应。在本研究中，我们分析了绝经前和绝经后女性及男性的人骨细胞对植物雌激素的反应。在用E₂（30 nM）、大豆苷元（D，3000 nM）、染料木黄酮（G，3000 nM）和Ral（3000 nM）处理后，绝经前女性来源的骨细胞对CK的刺激作用比绝经后女性来源的细胞更强；而对生物链菌素A（BA 3000 nM）、槲皮素（Qu 3000 nM）或G的羧基衍生物（cG 300 nM）的反应不依赖年龄。男性来源的细胞对植物雌激素无反应。当两个年龄组女性骨骼来源的细胞用JKF预处理，每天添加1 nM，持续3天时，对E₂、Ral、G和D的反应上调，但对BA或Qu无上调。（³）[H] E₂的核结合是不同植物雌激素的特征，用JKF预处理后特异性结合增加。相反，E₂ - Ov - Eu的膜结合对除Ral外的雌激素化合物具有特异性，用JKF预处理可抑制其结合，但ICI 161480（ICI）除外。男性骨细胞不结合E₂ - Ov - Eu但结合T - BSA - Eu；这种结合在用JKF预处理后被消除。用JKF预处理可增加两个年龄组女性和男性骨细胞中ERα的mRNA表达，降低ERβ的mRNA表达，所有这些细胞均表达两种ER，绝经前ERα与ERβ的比例为121:1，绝经后为78:1，男性骨细胞为105:1。本研究提出了联合使用维生素D类似物和植物雌激素进行激素替代疗法以预防绝经后骨质疏松症的可能性，这是动物模型中正在进行的研究课题。
