Lea C K, Flanagan A M
Department of Histopathology, Imperial College School of Medicine at St. Mary's, London, United Kingdom.
Am J Physiol. 1998 Feb;274(2):E328-35. doi: 10.1152/ajpendo.1998.274.2.E328.
The effect of androstenedione (ADIONE) slow-release pellets on cancellous bone volume (BV/TV) at the tibial metaphysis was investigated in ovariectomized (OVX) rats at various times from 21 to 180 days. Plasma levels of ADIONE and testosterone (T) in OVX rats were significantly reduced at 21 days and were restored close to levels in the sham rats with the 1.5-mg ADIONE pellet. OVX animals with and without ADIONE pellets resulted in close to a 50% reduction in BV/TV, by day 21. By day 180, OVX rats had only approximately 5% BV/TV, whereas that in ADIONE-treated OVX rats was significantly greater at approximately 12%. The reduced BV/TV was associated with increased bone resorption and formation. In a separate 90-day experiment, we found that the antiandrogen, Casodex, abrogated the ADIONE-induced skeletal-protective effect in OVX rats, whereas the antiaromatase, Arimidex, had no effect. This provides evidence that ADIONE protects against the development of osteopenia in the estrogen-deficient rat and mediates its effect through androgens and not estrogens.
在21至180天的不同时间点，研究了雄烯二酮（ADIONE）缓释微丸对去卵巢（OVX）大鼠胫骨近端松质骨体积（BV/TV）的影响。在21天时，OVX大鼠的血浆ADIONE和睾酮（T）水平显著降低，而植入1.5mg ADIONE微丸后，其水平恢复至接近假手术大鼠的水平。到21天时，无论有无ADIONE微丸，OVX动物的BV/TV均降低了近50%。到180天时，OVX大鼠的BV/TV仅约为5%，而接受ADIONE治疗的OVX大鼠的BV/TV显著更高，约为12%。BV/TV的降低与骨吸收和形成增加有关。在另一个为期90天的实验中，我们发现抗雄激素药物比卡鲁胺消除了ADIONE对OVX大鼠的骨骼保护作用，而抗芳香化酶药物阿那曲唑则没有效果。这表明ADIONE可预防雌激素缺乏大鼠骨质疏松症的发生，且其作用是通过雄激素而非雌激素介导的。
