Flutamide‐mediated androgen blockade evokes osteopenia in the female rat
Flutamide‐mediated androgen blockade evokes osteopenia in the female rat
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氟他胺介导的雄激素阻断引起雌性大鼠骨质减少
DOI：
10.1002/jbmr.5650080615
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发表时间：
1993
影响因子：
6.2
通讯作者：
E. Gold
中科院分区：
文献类型：
--
作者：
A. Goulding;E. Gold
雄激素被认为在女性和男性的骨骼构建和维持中起作用。抗雄激素药物氟替卡松抑制性腺和肾上腺对雄激素的反应。抗雄激素在体外可阻止雄激素刺激骨细胞增殖和分化，但雄激素阻断剂对体内骨代谢的影响尚未得到证实。本研究旨在确定（1）卵巢完整的雌性大鼠和（2）使用促黄体激素释放激素（LHRH）激动剂布舍瑞林（25 μg/kg体重/天SC）造成雌激素缺乏的大鼠中，氟替卡松（15 mg/kg体重/天经口）雄激素阻断是否会影响骨转换或骨组成。对4组45 Ca标记骨骼的大鼠进行了为期4周的研究：A组，安慰剂; B组，布舍瑞林; C组，氟吡格雷; D组，氟吡格雷+布舍瑞林。A-D组的全身钙值（平均值± SD）分别为（mg）2007 ± 109、1779 ± 138（与A组相比P <0.01）、1818 ± 140（与A组相比P <0.01）和1690 ± 75（与A组相比P < 0.01）。因此，布舍瑞林和氟吡格雷均诱导骨质减少。Skeleton 45 Ca变化表明布舍瑞林介导的雌激素缺乏性骨丢失是由于骨吸收增加，但氟骨苷介导的雄激素缺乏性骨变薄主要是由于骨形成减少。这些发现支持了雄激素在雌性大鼠骨量保存中发挥重要作用的观点。重要的是，足够的雌激素状态不能补偿氟骨水泥介导的骨质减少。虽然这项工作是在动物模型中完成的，但抗雄激素药物似乎可能会导致人类和大鼠的骨质减少。在女性中进一步研究雄激素可能的骨保护作用也是必要的。
Androgens are believed to play a role in building and maintaining bone in the female, as well as in the male. The antiandrogen drug flutamide inhibits responses to androgens from both the gonads and the adrenals. Antiandrogens prevent androgens stimulating bone cell proliferation and differentiation in vitro, but effects of androgen blockade on bone metabolism in vivo have not been tested. The present study was undertaken to determine whether androgen blockade with flutamide (15 mg/kg body weight orally daily) would influence bone turnover or bone composition (1) in female rats with intact ovaries and (2) in rats made estrogen‐deficient with the luteinizing hormone releasing hormone (LHRH) agonist, buserelin (25 μg/kg body weight per day SC). Four groups of rats with 45Ca‐labeled skeletons were studied for 4 weeks: group A, placebo; group B, buserelin; group C, flutamide; group D, flutamide + buserelin. Total‐body calcium values (mean ± SD) were (mg) 2007 ± 109, 1779 ± 138 (P < 0.01 versus group A), 1818 ± 140 (P < 0.01 versus group A), and 1690 ± 75 (P < 0.01 versus group A) in groups A‐D, respectively. Thus both buserelin and flutamide induced osteopenia. Skeletal 45Ca changes suggested buserelin‐mediated estrogen deficiency bone loss was due to increased bone resorption, but flutamide‐mediated androgen deficiency bone thinning was caused principally by reduced bone formation. These findings support the view that androgens play an important role in preserving bone mass in the female rat. Importantly, adequate estrogen status did not compensate for flutamide‐mediated osteopenia. Although this work was done in an animal model, it seems possible that antiandrogen drugs cause osteopenia in people as well as in the rat. Further study of the likely bone‐protective effects of androgen are also warranted in women.
影响因子：
5.8
作者：
FINKELSTEIN, JS;KLIBANSKI, A;CROWLEY, WF
通讯作者：
CROWLEY, WF