Hertrampf T, Schleipen B, Velders M, Laudenbach U, Fritzemeier K H, Diel P
Institut für Kreislaufforschung und Sportmedizin, Abt. molekulare und zelluläre Sportmedizin, DSHS Köln, Germany.
Mol Cell Endocrinol. 2008 Sep 10;291(1-2):104-8. doi: 10.1016/j.mce.2008.03.003. Epub 2008 Mar 16.
To further elucidate the processes involved in the physiology of bone-protection by estrogens, ovariectomized (OVX) rats were treated subcutaneously with 17beta-estradiol (E(2)), the ERalpha-specific agonist (16alpha-LE2) and the ERbeta-specific agonist (8beta-VE2). OVX and intact animals served as controls. Biomarkers of bone-formation (osteocalcin (OC), osteopontin (OPN)) and bone-resorption (telopeptides of collagen type I (CTx), pyridinoline cross-links (Pyd)) were quantified. Bone mineral density was measured by computed tomography. OVX-induced bone loss could be antagonized by subcutaneous administration of 17beta-estradiol and 16alpha-LE2. Serum levels of CTx, OC and OPN were significantly elevated in OVX compared to intact animals and reduced by 17beta-estradiol and 16alpha-LE2. Treatment of OVX rats with 8beta-VE2 did not affect bone mineral density (BMD) or bone-marker serum levels. Taken together, the complex expression pattern of bone-markers in OVX rats following subcutaneous administration of ER subtype-specific agonists indicates that 17beta-estradiol exerts its bone-protective effects by modulating the activity of osteoclasts and osteoblasts via ERalpha.
为了进一步阐明雌激素保护骨骼生理过程中涉及的机制，对去卵巢（OVX）大鼠皮下注射17β-雌二醇（E₂）、雌激素受体α（ERα）特异性激动剂（16α-LE2）和雌激素受体β（ERβ）特异性激动剂（8β-VE2）。OVX大鼠和未处理的大鼠作为对照。对骨形成生物标志物（骨钙素（OC）、骨桥蛋白（OPN））和骨吸收生物标志物（I型胶原端肽（CTx）、吡啶啉交联物（Pyd））进行定量分析。通过计算机断层扫描测量骨密度。皮下注射17β-雌二醇和16α-LE2可对抗OVX诱导的骨质流失。与未处理的大鼠相比，OVX大鼠血清中CTx、OC和OPN水平显著升高，而17β-雌二醇和16α-LE2可使其降低。用8β-VE2处理OVX大鼠不影响骨密度（BMD）或骨标志物血清水平。综上所述，皮下注射ER亚型特异性激动剂后OVX大鼠骨标志物的复杂表达模式表明，17β-雌二醇通过ERα调节破骨细胞和成骨细胞的活性发挥其骨骼保护作用。
