Lea C K, Moxham V, Reed M J, Flanagan A M
Department of Histopathology, Imperial College of Medicine at St Mary's, London, UK.
J Endocrinol. 1998 Feb;156(2):331-9. doi: 10.1677/joe.0.1560331.
We have tested the hypothesis that androstenedione (administered as 21-day, slow-release pellets) is converted to active sex steroids and reduces bone turnover in the ovariectomised rat model. We found that ovariectomy resulted in a minor but significant reduction in plasma concentrations of androstenedione and testosterone and a more significant reduction in oestrone (E1) and oestradiol (E2). This was associated with the expected substantial loss of metaphyseal cancellous bone volume. Androstenedione (1.5-100 mg) pellets increased the plasma concentrations of androstenedione and testosterone above those in the ovariectomised (ovx) rats in a dose-responsive manner, whereas E2 plasma concentrations were increased to a minor but significant degree above those in the ovx animals. Androstenedione reduced loss of cancellous bone volume in a dose-dependent fashion by reducing bone turnover. The 1.5, 5 and 100 mg androstenedione-induced effect on bone turnover was not abrogated by simultaneous treatment with Arimidex, an aromatase inhibitor. This implies that the skeletal-protective effect of androstenedione was not oestrogen-mediated.
我们已经验证了这样一个假设，即雄烯二酮（以21天缓释微丸形式给药）可转化为活性甾体性激素，并降低去卵巢大鼠模型中的骨转换率。我们发现，去卵巢导致雄烯二酮和睾酮的血浆浓度出现轻微但显著的降低，而雌酮（E1）和雌二醇（E2）的降低更为显著。这与预期的干骺端松质骨体积的大量减少相关。雄烯二酮（1.5 - 100毫克）微丸以剂量反应方式使雄烯二酮和睾酮的血浆浓度高于去卵巢（ovx）大鼠，而E2血浆浓度虽有轻微升高但也显著高于ovx动物。雄烯二酮通过降低骨转换以剂量依赖方式减少松质骨体积的丢失。同时使用芳香化酶抑制剂阿那曲唑治疗并不能消除1.5、5和100毫克雄烯二酮对骨转换的诱导作用。这意味着雄烯二酮的骨骼保护作用不是由雌激素介导的。
