Wu Jianyao, Movérare-Skrtic Sofia, Börjesson Anna E, Lagerquist Marie K, Sjögren Klara, Windahl Sara H, Koskela Antti, Grahnemo Louise, Islander Ulrika, Wilhelmson Anna S, Tivesten Åsa, Tuukkanen Juha, Ohlsson Claes
Centre for Bone and Arthritis Research (J.W., S.M.-S., A.E.B., M.K.L., K.S., S.H.W., L.G., U.I., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, S-413 45 Gothenburg, Sweden; Rheumatology and Bone Diseases Unit (A.E.B.), Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, Scotland, United Kingdom; Centre for Comparative and Clinical Anatomy (S.H.W.), School of Veterinary Science, University of Bristol, Bristol BS28EJ, United Kingdom; Department of Anatomy and Cell Biology (A.K., J.T.), Medical Research Center, University of Oulu, FI-90014 Oulu, Finland; and The Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., ÅT.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
Endocrinology. 2016 Feb;157(2):969-77. doi: 10.1210/en.2015-1566. Epub 2015 Nov 20.
Testosterone is a crucial regulator of the skeleton, but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg·d of enzalutamide for 21 days or were surgically castrated and were compared with vehicle-treated gonadal intact mice. Although orchidectomy reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orchidectomy reduced the bone mass in the axial skeleton as demonstrated by a reduced lumbar spine areal bone mineral density (P < .001) and trabecular bone volume fraction in L5 vertebrae (P < .001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure -15.3% ± 3.5%; P < .01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR.
睾酮是骨骼的关键调节因子，但雄激素受体（AR）在维持成年男性骨骼方面的作用尚不清楚。在本研究中，通过恩杂鲁胺评估了AR在性成熟后对骨代谢和骨骼生长的作用，恩杂鲁胺是一种用于治疗前列腺癌患者的新型AR拮抗剂。给9周龄雄性小鼠每日腹腔注射10、30或100 mg/kg恩杂鲁胺，持续21天，或进行手术去势，并与给予赋形剂的性腺完整小鼠进行比较。虽然去势降低了附肢骨骼的皮质骨厚度和小梁骨体积分数，但这些参数不受恩杂鲁胺的影响。相比之下，与给予赋形剂的性腺完整小鼠相比，恩杂鲁胺和去势均降低了轴向骨骼的骨量，表现为腰椎面骨矿物质密度降低（P < 0.001）和L5椎骨小梁骨体积分数降低（P < 0.001）。L5椎骨的压缩试验显示，恩杂鲁胺显著降低了轴向骨骼的机械强度（破坏时的最大负荷 -15.3% ± 3.5%；P < 0.01）。恩杂鲁胺对轴向骨骼的影响与高骨转换有关。总之，恩杂鲁胺降低了性成熟后雄性小鼠轴向骨骼而非附肢骨骼的骨量。我们认为，睾酮对雄性小鼠轴向骨骼的作用主要通过AR介导。
