Bone has a sexually dimorphic response to aromatase deficiency
Bone has a sexually dimorphic response to aromatase deficiency
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DOI：
10.1359/jbmr.2000.15.3.507
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发表时间：
2000-03-01
影响因子：
6.2
通讯作者：
Simpson, ER
中科院分区：
文献类型：
--
作者：
Öz, OK;Zerwekh, JE;Simpson, ER
芳香酶从雄激素前体合成雌激素。为了更好地理解雌激素在骨骼代谢和生长中的作用，我们评估了芳香酶缺陷（ArKO）小鼠的长骨生长和组织形态计量学。动物的年龄范围为5-7个月。在这个年龄段，小鼠已经达到了骨密度峰值，但骨生长仍然缓慢。股骨长度，长骨生长的指数，显示下降的增长与野生型（wt）同窝仔相比，在ArKO男性，但没有显着差异的女性。放射学上，与年龄和性别匹配的同窝仔相比，ArKO雄性和雌性均显示腰椎骨质减少。在组织学上，ArKO雄性和雌性动物均显示出骨小梁型图片，其特征在于骨小梁体积和骨小梁厚度显著降低。然而，与野生型同窝出生的雌性ArKO动物相比，显示出与骨转换增加一致的骨重建图像，非常类似于人类的早期绝经后骨质疏松症。另一方面，雄性ArKO动物与野生型同窝小鼠相比，成骨细胞和骨细胞表面均显示出减少，类似于年龄相关的骨质减少。这些发现表明，在芳香化酶缺陷小鼠中观察到的骨质疏松症可能源于雄性和雌性之间不同的骨重塑活动。这些结果也表明，ArKO模型表现出预期的结果，雌激素缺乏，并可能是一个很好的模型，研究性别特异性反应，雌激素缺乏。此外，它们暗示雌激素对于雄性和雌性小鼠达到峰值骨量是重要的。
Aromatase synthesizes estrogen from androgen precursors, To better understand the role of estrogen in skeletal metabolism and growth, we have assessed long bone growth and histomorphometry in aromatase deficient (ArKO) mice. The age range for the animals was 5-7 months. At this age mice have already achieved peak bone density but continue slow bone growth. Femur length, an index of long bone growth, showed decreased growth in ArKO males compared with wild-type (wt) littermates but no significant difference in females. Radiographically, compared with age- and sex- matched littermates both ArKO males and females showed osteopenia in the lumbar spine. Histologically, both ArKO males and females showed an osteoporotic-type picture, characterized by significant decreases in trabecular bone volume and trabecular thickness. However, compared with wt littermates female ArKO animals showed a bone remodeling picture consistent with increased bone turnover, much like early postmenopausal osteoporosis in humans. On the other hand, male ArKO animals showed decreases in both osteoblastic and osteoclastic surfaces compared with wt littermates, similar to age-related osteopenia, These findings suggest that osteoporosis seen in aromatase-deficient mice may arise from different bone remodeling activities between males and females. These results also show that the ArKO model exhibits the expected results of estrogen deficiency and may be a good model for investigating sex-specific responses to estrogen deficiency. Furthermore, they imply that estrogen is important for attaining peak bone mass in male as well as in female mice.