Vandenput Liesbeth, Swinnen Johannes V, Boonen Steven, Van Herck Erik, Erben Reinhold G, Bouillon Roger, Vanderschueren Dirk
Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven B-3000, Belgium.
J Bone Miner Res. 2004 Sep;19(9):1462-70. doi: 10.1359/JBMR.040505. Epub 2004 May 10.
The role of androgen receptor-mediated androgen action on bone was investigated in testicular feminized male (Tfm) mice. Cortical bone was found to be unresponsive to testosterone (T) in orchidectomized Tfm mice, whereas cortical thickness as well as trabecular BMD and structure were fully maintained by T in the corresponding Tabby control mice. These data show an essential role for androgen receptor-mediated androgen action in periosteal bone formation.
Androgens can affect the male skeleton both directly-through activation of the androgen receptor (AR)-and indirectly-through stimulation of estrogen receptors after aromatization. We assessed the importance of AR-mediated androgen action on bone in a mouse model of androgen resistance.
Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet. A comprehensive analysis of the skeletal effects of androgen deficiency and replacement was performed using histomorphometry, QCT, and biochemical assessment of bone turnover.
As expected, T increased trabecular BMD, volume, number, and width in ORX Tabby mice. In ORX Tfm mice, however, T had less effect on trabecular BMD and no effect on trabecular bone structure. T action on trabecular bone was associated with opposite changes in bone turnover: trabecular and endocortical bone turnover and serum levels of osteocalcin were all reduced by T in ORX Tabby mice, but not in ORX Tfm mice. T also increased cortical thickness (+16%), area, and density in ORX Tabby mice, but not in Tfm mice, resulting in greater bone strength in the Tabby control strain. The positive effects of T on cortical bone reflected a stimulatory effect on periosteal bone formation (+137%), which was again absent in Tfm mice.
These data show that, in male mice, AR-mediated T action is essential for periosteal bone formation and contributes to trabecular bone maintenance.
在睾丸雌性化雄性（Tfm）小鼠中研究了雄激素受体介导的雄激素对骨骼的作用。在去势的Tfm小鼠中，皮质骨对睾酮（T）无反应，而在相应的虎斑对照小鼠中，T可完全维持皮质厚度以及小梁骨密度和结构。这些数据表明雄激素受体介导的雄激素作用在骨膜骨形成中起重要作用。
雄激素可通过激活雄激素受体（AR）直接影响男性骨骼，并通过芳香化作用刺激雌激素受体间接影响男性骨骼。我们在雄激素抵抗小鼠模型中评估了AR介导的雄激素对骨骼作用的重要性。
将8周龄的雄激素抵抗性睾丸雌性化雄性（Tfm）小鼠和虎斑对照小鼠去势（ORX），并用缓释睾酮（T）丸（每天释放167微克）或安慰剂丸治疗4周。使用组织形态计量学、定量计算机断层扫描（QCT）和骨转换的生化评估对雄激素缺乏和替代的骨骼效应进行了全面分析。
正如预期的那样，T增加了去势虎斑小鼠的小梁骨密度、体积、数量和宽度。然而，在去势Tfm小鼠中，T对小梁骨密度的影响较小，对小梁骨结构没有影响。T对小梁骨的作用与骨转换的相反变化有关：去势虎斑小鼠中，T降低了小梁和内皮质骨转换以及骨钙素血清水平，但在去势Tfm小鼠中没有。T还增加了去势虎斑小鼠的皮质厚度（+16%）、面积和密度，但在Tfm小鼠中没有，从而使虎斑对照品系的骨强度更高。T对皮质骨的积极作用反映了对骨膜骨形成的刺激作用（+137%），而Tfm小鼠中再次没有这种作用。
这些数据表明，在雄性小鼠中，AR介导的T作用对骨膜骨形成至关重要，并有助于小梁骨的维持。
