Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.
Cells. 2019 Oct 25;8(11):1318. doi: 10.3390/cells8111318.
Androgens are not only essential for bone development but for the maintenance of bone mass. Therefore, conditions with androgen deficiency, such as male hypogonadism, androgen-insensitive syndromes, and prostate cancer with androgen deprivation therapy are strongly associated with bone loss and increased fracture risk. Here we summarize the skeletal effects of androgens-androgen receptors (AR) actions based on in vitro and in vivo studies from animals and humans, and discuss bone loss due to androgens/AR deficiency to clarify the molecular basis for the anabolic action of androgens and AR in bone homeostasis and unravel the functions of androgen/AR signaling in healthy and disease states. Moreover, we provide evidence for the skeletal benefits of androgen therapy and elucidate why androgens are more beneficial than male sexual hormones, highlighting their therapeutic potential as osteoanabolic steroids in improving bone fracture repair. Finally, the application of selective androgen receptor modulators may provide new approaches for the treatment of osteoporosis and fractures as well as building stronger bones in diseases dependent on androgens/AR status.
雄激素不仅对骨骼发育至关重要,而且对维持骨量也至关重要。因此,雄激素缺乏症,如男性性腺功能减退症、雄激素不敏感综合征和前列腺癌的去势治疗,与骨丢失和骨折风险增加密切相关。在这里,我们根据动物和人类的体外和体内研究,总结了雄激素-雄激素受体 (AR) 作用对骨骼的影响,并讨论了由于雄激素/AR 缺乏导致的骨丢失,以阐明雄激素和 AR 在骨稳态中的合成代谢作用的分子基础,并阐明雄激素/AR 信号在健康和疾病状态下的功能。此外,我们为雄激素治疗的骨骼益处提供了证据,并阐明了为什么雄激素比男性性激素更有益,突出了它们作为改善骨骨折修复的骨合成代谢类固醇的治疗潜力。最后,选择性雄激素受体调节剂的应用可能为治疗骨质疏松症和骨折以及在依赖雄激素/AR 状态的疾病中增强骨骼提供新的方法。