Vanderschueren D, Van Herck E, De Coster R, Bouillon R
Laboratorium voor Experimentele Geneeskunde en Endocrinologie (LEGENDO), Onderwijs en Navorsing, Gasthuisberg, B-3000 Leuven, Belgium.
Calcif Tissue Int. 1996 Sep;59(3):179-83. doi: 10.1007/s002239900106.
A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance.
将非甾体类芳香化酶抑制剂伏洛唑（VOR）给予12月龄的雄性Wistar大鼠，并将其效果与雄激素缺乏的效果进行比较。大鼠进行假手术（SHAM）或去势手术（ORCH），并分别给予或不给予VOR治疗。由此，创建了四个实验组（SHAM、ORCH、SHAM + VOR、ORCH + VOR）。随访期为4个月。在实验期结束时，用双能X线吸收法体外测量前四个腰椎和右股骨的骨矿物质密度（BMD），通过血清骨钙素评估骨形成，通过尿中（脱氧）吡啶啉排泄评估骨吸收。去势手术使骨吸收增加了2至3倍，而骨形成仅略有增加。用VOR治疗完整雄性大鼠也增加了骨吸收（增加30%），而在这个SHAM + VOR组中骨形成并未增加。与未接受VOR的SHAM组相比，它们的股骨BMD降低了7%（P < 0.01），腰椎BMD降低了6%（P < 0.01）。此外，骨矿物质密度的这种降低与ORCH组中观察到的预期骨密度降低（6 - 10%）没有显著差异。这也反映在与SHAM组相比，SHAM + VOR组前四个腰椎的钙含量降低了15%（P < 0.001），ORCH组降低了9 - 14%（P < 0.05）。因此，这些数据表明，抑制雄激素向雌激素的芳香化作用会增加骨吸收和骨质流失，类似于完全去除雄激素后观察到的情况。雄激素向雌激素的芳香化作用因此可能至少部分解释了雄激素对骨骼维持的作用。
