Sinnesael Mieke, Boonen Steven, Claessens Frank, Gielen Evelien, Vanderschueren Dirk
Experimental Medicine and Endocrinology, Department of Experimental Medicine, K. U. Leuven, 300 Leuven, Belgium.
J Osteoporos. 2011;2011:240328. doi: 10.4061/2011/240328. Epub 2011 Sep 14.
Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.
睾酮是男性骨骼生长和维持的重要激素。性腺功能减退的男性骨转换加速，骨折风险增加。在这些男性中，给予睾酮可抑制骨吸收并维持骨量。然而，睾酮在包括男性骨骼在内的许多组织中通过芳香化作用转化为雌二醇。一些患有雌激素受体α或芳香化酶失活突变的男性病例凸显了雌激素受体α激活以及雄激素芳香化为雌激素的重要性。所有这些男性通常骨量低、骨转换高且骨骺未闭合。与这些发现一致，队列研究证实，雌二醇在达到峰值骨量后有助于维持骨量，且老年男性的雌二醇与骨折之间存在关联。最近对基因敲除小鼠的研究增进了我们对雄激素和雌激素在不同骨区室中作用的理解。雌激素受体激活而非雄激素受体激活参与小鼠雄性纵向附属骨骼生长的调节。雄激素和雌激素受体均可独立介导雄性小鼠中类固醇对松质骨的保护作用。对雄性小鼠成骨细胞中雄激素受体的选择性基因敲除研究表明，成骨细胞是雄激素受体介导维持小梁骨体积以及协调骨基质合成与矿化的靶细胞。综上所述，人类和动物研究均表明，睾酮通过雄激素和雌激素受体对不同骨表面具有双重作用模式。
