Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
J Endocrinol. 2010 Jul;206(1):93-103. doi: 10.1677/JOE-10-0026. Epub 2010 Apr 15.
We used our genomic androgen receptor (AR) knockout (ARKO) mouse model, in which the AR is unable to bind DNA to: 1) document gender differences between males and females; 2) identify the genomic (DNA-binding-dependent) AR-mediated actions in males; 3) determine the contribution of genomic AR-mediated actions to these gender differences; and 4) identify physiological genomic AR-mediated actions in females. At 9 weeks of age, control males had higher body, heart and kidney mass, lower spleen mass, and longer and larger bones compared to control females. Compared to control males, ARKO males had lower body and kidney mass, higher splenic mass, and reductions in cortical and trabecular bone. Deletion of the AR in ARKO males abolished the gender differences in heart and cortical bone. Compared with control females, ARKO females had normal body weight, but 14% lower heart mass and heart weight/body weight ratio. Relative kidney mass was also reduced, and relative spleen mass was increased. ARKO females had a significant reduction in cortical bone growth and changes in trabecular architecture, although with no net change in trabecular bone volume. In conclusion, we have shown that androgens acting via the genomic AR signaling pathway mediate, at least in part, the gender differences in body mass, heart, kidney, spleen, and bone, and play a physiological role in the regulation of cardiac, kidney and splenic size, cortical bone growth, and trabecular bone architecture in females.
我们使用了我们的基因组雄激素受体 (AR) 敲除 (ARKO) 小鼠模型，在该模型中，AR 无法与 DNA 结合：1) 记录雄性和雌性之间的性别差异；2) 确定雄性中基因组 (DNA 结合依赖性) AR 介导的作用；3) 确定基因组 AR 介导的作用对这些性别差异的贡献；4) 确定雌性中的生理基因组 AR 介导的作用。在 9 周龄时，与对照组雌性相比，对照组雄性的体重、心脏和肾脏质量更高，脾脏质量更低，骨骼更长更大。与对照组雄性相比，ARKO 雄性的体重和肾脏质量更低，脾脏质量更高，皮质骨和小梁骨减少。在 ARKO 雄性中删除 AR 消除了心脏和皮质骨的性别差异。与对照组雌性相比，ARKO 雌性的体重正常，但心脏质量和心脏重量/体重比低 14%。相对肾脏质量也降低，相对脾脏质量增加。尽管小梁骨体积没有净变化，但 ARKO 雌性的皮质骨生长和小梁结构发生了变化。总之，我们已经表明，雄激素通过基因组 AR 信号通路介导，至少部分介导了体重、心脏、肾脏、脾脏和骨骼的性别差异，并在调节心脏、肾脏和脾脏大小、皮质骨生长和小梁骨结构方面发挥了生理作用在女性中。
