Sims Natalie A, Brennan Karen, Spaliviero Jenny, Handelsman David J, Seibel Markus J
Department of Medicine at St. Vincent's Hospital, the University of Melbourne and St. Vincent's Institute, Fitzroy, Victoria, Australia.
Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E456-62. doi: 10.1152/ajpendo.00311.2005. Epub 2005 Oct 4.
Although testosterone (T) has striking effects on mature skeletal size and structure, it is not clear whether this depends exclusively on adult circulating levels of T or whether additional early-life factors also play a role. We have compared the androgen-deficient hypogonadal (hpg) mutant mouse with intact, orchidectomized, and T-treated non-hpg mice to determine relative contributions of adult and perinatal T to bone growth and development. At 3 wk of age, although trabecular and cortical bone structure was normal, bone turnover was significantly altered in hpg male mice; osteoid volume (OV/BV) and osteoblast surface (ObS/BS) were significantly lower and osteoclast surface (OcS/BS) significantly higher in hpg mice compared with age-matched non-hpg mice, pointing to a role for the perinatal T surge in determining bone turnover levels before sexual maturity. At 9 wk of age, the hpg bone phenotype mimicked closely that of age-matched non-hpg mice that had been orchidectomized at 3 wk of age, including low trabecular bone mass and high bone turnover. These bone phenotypes of hpg and orchidectomized non-hpg mice were all prevented by replacement doses of T or dihydrotestosterone (DHT), suggesting that these are determined by adult sex steroid hormones. In contrast, a short bone phenotype that could not be prevented by T or DHT treatment was observed in 9-wk-old hpg mice yet not in intact or castrated non-hpg mice. These data suggest a role for the perinatal T surge in determining adult bone length and confirms that adult circulating T determines adult bone density.
尽管睾酮（T）对成熟骨骼的大小和结构有显著影响，但尚不清楚这是否仅取决于成年期循环中的T水平，还是早期生活中的其他因素也起作用。我们将雄激素缺乏的性腺功能减退（hpg）突变小鼠与完整、去势和接受T治疗的非hpg小鼠进行了比较，以确定成年期和围生期T对骨骼生长和发育的相对贡献。在3周龄时，尽管hpg雄性小鼠的小梁骨和皮质骨结构正常，但其骨转换明显改变；与年龄匹配的非hpg小鼠相比，hpg小鼠的类骨质体积（OV/BV）和成骨细胞表面（ObS/BS）显著降低，破骨细胞表面（OcS/BS）显著升高，这表明围生期T高峰在决定性成熟前的骨转换水平中起作用。在9周龄时，hpg小鼠的骨表型与3周龄时去势的年龄匹配非hpg小鼠的骨表型非常相似，包括低小梁骨量和高骨转换。hpg小鼠和去势非hpg小鼠的这些骨表型均通过补充剂量的T或双氢睾酮（DHT）得以预防，这表明这些表型是由成年期性类固醇激素决定的。相比之下，在9周龄的hpg小鼠中观察到一种短骨表型，T或DHT治疗无法预防，而在完整或去势的非hpg小鼠中未观察到。这些数据表明围生期T高峰在决定成年骨长度方面起作用，并证实成年期循环中的T决定成年骨密度。
