Effects of alcohol on skeletal response to growth hormone in hypophysectomized rats.

Effects of alcohol on skeletal response to growth hormone in hypophysectomized rats.
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DOI:
10.1016/j.bone.2009.10.027
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发表时间:
2010-03
期刊:
影响因子:
4.1
通讯作者:
Iwaniec, Urszula T.
Iwaniec, Urszula T.
中科院分区:
医学2区
文献类型:
--
作者:
Turner, Russell T.;Rosen, Clifford J.;Iwaniec, Urszula T.

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长期酗酒是导致骨质疏松症的公认危险因素。然而,骨丢失的确切机制在很大程度上尚不清楚。酒精降低胰岛素样生长因子-I(IGF-I)的骨骼表达,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GH缺陷型雄性SD大鼠(HYPOX)骨骼的影响。将3月龄大鼠分为4组:正常对照组、HYPOX组、HYPOX+GH组和HYPOX+酒精+GH组。术后6天,所有动物均转为流质饮食。酒精喂养组在手术后11天开始适应酒精的逐步增加。在最后8天的研究中给予生长激素或赋形剂,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组的纵向骨生长和松质骨形成较低。后者与较低的矿化周长/骨周长相关。HYPOX治疗后骨髓肥胖率较高。与HYPOX相比,GH治疗增加了体重增加和骨形成率,并降低了骨髓肥胖率。与不饮酒的生长激素治疗效果相比,HYPOX和酒精喂养的GH处理的HYPOX大鼠的骨髓肥胖症没有差异。酒精不改变生长激素诱导的体重增加或血清IGF-I水平的增加,但显着削弱生长激素对胫骨生长和松质骨形成的影响。我们的结论是,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通过骨骼对生长激素的抵抗来调节的。
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.
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发表时间: 1999-01-01
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发表时间: 2009-02
期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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