Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331, USA.
Bone. 2010 Mar;46(3):806-12. doi: 10.1016/j.bone.2009.10.027. Epub 2009 Oct 30.
Chronic alcohol abuse is an established risk factor for osteoporosis. However, the precise mechanisms for the bone loss are largely unknown. Alcohol decreases skeletal expression of insulin-like growth factor-I (IGF-I), an important growth hormone (GH)-regulated skeletal growth factor. Therefore, we investigated the effects of alcohol on the skeletal response to GH in male Sprague-Dawley rats made GH-deficient by hypophysectomy (HYPOX). Four groups of sexually mature (3-month-old) rats were studied: pituitary-intact (control), HYPOX, HYPOX + GH, and HYPOX + alcohol + GH. All animals were transferred to a liquid diet 6 days following surgery. The alcohol-fed group was adapted to a graded increase in alcohol beginning 11 days following surgery. GH or vehicle was administered during the final 8 days of study and all animals were sacrificed 25 days following surgery. HYPOX resulted in cessation of body weight gain and tibial growth. Compared to controls, longitudinal bone growth and cancellous bone formation were lower following HYPOX. The latter was associated with lower mineralizing perimeter/bone perimeter. Bone marrow adiposity was higher following HYPOX. Compared to HYPOX, GH treatment increased body weight gain and bone formation rate, and decreased bone marrow adiposity. In contrast to the effects of GH treatment without alcohol, bone marrow adiposity did not differ between HYPOX and alcohol-fed GH-treated HYPOX rats. Alcohol did not alter GH-induced weight gain or increases in serum IGF-I levels, but significantly impaired the effects of GH on tibial growth and cancellous bone formation. We conclude that the detrimental skeletal effects of alcohol abuse observed in this experiment are mediated, at least in part, by skeletal resistance to GH.
慢性酒精滥用是骨质疏松症的一个既定危险因素。然而，导致骨质流失的确切机制在很大程度上尚不清楚。酒精会降低胰岛素样生长因子-I（IGF-I）在骨骼中的表达，IGF-I 是一种重要的生长激素（GH）调节的骨骼生长因子。因此，我们研究了酒精对去垂体（HYPOX）雄性 Sprague-Dawley 大鼠骨骼对 GH 反应的影响。研究了四组性成熟（3 个月龄）大鼠：垂体完整（对照）、HYPOX、HYPOX+GH 和 HYPOX+酒精+GH。所有动物在手术后第 6 天转移到液体饮食。酒精喂养组在手术后第 11 天开始适应酒精的逐渐增加。在研究的最后 8 天给予 GH 或载体，所有动物在手术后 25 天被处死。HYPOX 导致体重增加和胫骨生长停止。与对照组相比，HYPOX 后纵向骨生长和松质骨形成减少。后者与较低的矿化周长/骨周长有关。骨髓脂肪含量在 HYPOX 后增加。与 HYPOX 相比，GH 治疗增加了体重增加和骨形成率，并降低了骨髓脂肪含量。与没有酒精的 GH 治疗的作用相反，HYPOX 和酒精喂养的 GH 治疗的 HYPOX 大鼠之间的骨髓脂肪含量没有差异。酒精并未改变 GH 诱导的体重增加或血清 IGF-I 水平的增加，但显著损害了 GH 对胫骨生长和松质骨形成的作用。我们得出结论，在本实验中观察到的酒精滥用对骨骼的有害影响至少部分是由骨骼对 GH 的抵抗介导的。
