Rosen H N, Tollin S, Balena R, Middlebrooks V L, Moses A C, Yamamoto M, Zeind A J, Greenspan S L
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts 02215.
Endocrinology. 1995 Apr;136(4):1381-7. doi: 10.1210/endo.136.4.7895648.
Bone is an androgen-dependent tissue. It is not known whether normal bony growth and mineralization in males is dependent on testosterone alone, or whether its metabolite, dihydrotestosterone (DHT), also is required. To answer this question, we examined the effect of finasteride, an inhibitor of DHT synthesis, on bone in rats. Three-month-old male rats were treated with placebo, finasteride, or orchidectomy. The bone mineral densities (BMD) of the spine and whole body were measured in vivo by dual x-ray absorptiometry at weeks 0 and 11, and the BMD of the femur and tibia were measured ex vivo at week 11. Histomorphometric analysis was performed on the proximal tibia at week 11. The increase in spine and whole body BMD in finasteride-treated rats did not differ from that in controls, whereas these values were significantly lower in orchidectomized rats. Similarly, the BMD of the femur and tibia and the cancellous bone volume of the proximal tibia in finasteride-treated rats did not differ from those in controls, whereas these values were significantly lower in orchidectomized rats. In summary, bone development and density were normal in rats treated with finasteride. We conclude that selective DHT deficiency is not deleterious to the male rat skeleton.
骨骼是一种雄激素依赖组织。目前尚不清楚男性正常的骨骼生长和矿化是否仅依赖于睾酮,还是其代谢产物双氢睾酮(DHT)也必不可少。为了回答这个问题,我们研究了DHT合成抑制剂非那雄胺对大鼠骨骼的影响。对3个月大的雄性大鼠给予安慰剂、非那雄胺或进行去势手术。在第0周和第11周通过双能X线吸收法在体内测量脊柱和全身的骨矿物质密度(BMD),并在第11周离体测量股骨和胫骨的BMD。在第11周对胫骨近端进行组织形态计量学分析。非那雄胺治疗组大鼠脊柱和全身BMD的增加与对照组无差异,而去势大鼠的这些值显著更低。同样,非那雄胺治疗组大鼠股骨和胫骨的BMD以及胫骨近端的松质骨体积与对照组无差异,而去势大鼠的这些值显著更低。总之,非那雄胺治疗的大鼠骨骼发育和密度正常。我们得出结论,选择性DHT缺乏对雄性大鼠骨骼无害。