Lea C K, Flanagan A M
Department of Histopathology, Imperial College of Science, Technology and Medicine at St Mary's, Norfolk Place, London, UK.
J Endocrinol. 1999 Jan;160(1):111-7. doi: 10.1677/joe.0.1600111.
We tested the hypothesis that ovarian androgens play a role in protecting against cancellous bone loss in oestrogen-deficient states and that conversion of androgens to oestrogens is not catalysed by aromatase P450 in the bone or bone-marrow microenvironment. We did this by administering the anti-oestrogen, ICI 182,780, alone and in combination with the anti-androgen, Casodex, and compared the effects on the skeleton with those of ovariectomy. We found that rats subjected to ovariectomy lost significantly greater cancellous bone volume compared with those treated with ICI 182,780, but that combination anti-oestrogen and anti-androgen therapy resulted in bone loss equivalent to that in ovariectomised animals. The skeletal-protective effect of preserving the ovaries in animals which had been chemically ovariectomised was attributed to suppression of osteoclast parameters. Taken together, these data suggest that a reduction in ovarian androgens accentuates the increase in osteoclast number and the reduction in cancellous bone volume which occurs in oestrogen-deficient states. Failure to detect transcripts for aromatase cytochrome P450 in the bone and bone-marrow of rats provides supportive evidence that androgens mediate their skeletal-protective effect directly and not by peripheral conversion to oestradiol.
在雌激素缺乏状态下，卵巢雄激素在防止松质骨丢失中发挥作用，并且雄激素向雌激素的转化并非由骨或骨髓微环境中的芳香化酶P450催化。我们通过单独给予抗雌激素药物ICI 182,780以及将其与抗雄激素药物康士得联合使用来进行验证，并将其对骨骼的影响与卵巢切除术的影响进行比较。我们发现，与接受ICI 182,780治疗的大鼠相比，接受卵巢切除术的大鼠松质骨体积显著减少，但抗雌激素与抗雄激素联合治疗导致的骨丢失与卵巢切除动物相当。在化学去卵巢的动物中保留卵巢的骨骼保护作用归因于破骨细胞参数的抑制。综上所述，这些数据表明，卵巢雄激素的减少加剧了雌激素缺乏状态下破骨细胞数量的增加和松质骨体积的减少。在大鼠的骨骼和骨髓中未能检测到芳香化酶细胞色素P450的转录本，这提供了支持性证据，表明雄激素直接介导其骨骼保护作用，而非通过外周转化为雌二醇来实现。
