Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-α
Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-α
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DOI：
10.1096/fj.08-113456
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Vanderschueren, Dirk
中科院分区：
文献类型：
--
作者：
Callewaert, Filip;Venken, Katrien;Vanderschueren, Dirk
骨质疏松症和肌肉无力是老年男性的重要健康问题，可能部分与生物雄激素活性有关。这种雄激素作用可通过刺激雄激素受体（AR）直接介导，或通过在雄激素芳构化为雌激素后刺激雌激素受体-α（ER α）间接介导。为了评估AR和ER α途径对骨和身体组成的差异作用，产生并表征AR-ER α双敲除小鼠。AR破坏降低了骨小梁质量，而ER α破坏对AR依赖性骨小梁丢失没有额外的影响。相反，与单独的AR或ER α破坏相比，AR和ER α联合失活还减少了皮质骨和肌肉质量。ER α失活-在存在或不存在AR的情况下-增加脂肪量。我们证明，AR激活是唯一负责的发展和维持男性小梁骨量。然而，需要AR和ER α激活来优化皮质骨和肌肉质量的获取。单独的ER α激活足以调节脂肪量。我们的研究结果清楚地定义了AR和ER α信号对雄性小鼠小梁和皮质骨量以及身体组成的相对重要性。Callewaert，F.，Venken，K.，Ophoff，J.，De Gendt，K.，Torcasio，A.，货车Lenthe，G. H、货车Oosterwyck，H.，Boonen，S.，肉汤河，Verhoeven，G.，Vanderschueren，D.雄激素和雌激素受体α联合失活对雄性小鼠骨和身体组成的差异调节。FASEB J. 23，232-240（2009）
Osteoporosis and muscle frailty are important health problems in elderly men and may be partly related to biological androgen activity. This androgen action can be mediated directly through stimulation of the androgen receptor (AR) or indirectly through stimulation of estrogen receptor-alpha (ER alpha) following aromatization of androgens into estrogens. To assess the differential action of AR and ER alpha pathways on bone and body composition, AR-ER alpha double-knockout mice were generated and characterized. AR disruption decreased trabecular bone mass, whereas ER alpha disruption had no additional effect on the AR-dependent trabecular bone loss. In contrast, combined AR and ER alpha inactivation additionally reduced cortical bone and muscle mass compared with either AR or ER alpha disruption alone. ER alpha inactivation-in the presence or absence of AR-increased fat mass. We demonstrate that AR activation is solely responsible for the development and maintenance of male trabecular bone mass. Both AR and ER alpha activation, however, are needed to optimize the acquisition of cortical bone and muscle mass. ER alpha activation alone is sufficient for the regulation of fat mass. Our findings clearly define the relative importance of AR and ER alpha signaling on trabecular and cortical bone mass as well as body composition in male mice.-Callewaert, F., Venken, K., Ophoff, J., De Gendt, K., Torcasio, A., van Lenthe, G. H., Van Oosterwyck, H., Boonen, S., Bouillon, R., Verhoeven, G., Vanderschueren, D. Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-alpha. FASEB J. 23, 232-240 (2009)