Effects of Alcohol and Estrogen Receptor Blockade Using ICI 182,780 on Bone in Ovariectomized Rats.
Effects of Alcohol and Estrogen Receptor Blockade Using ICI 182,780 on Bone in Ovariectomized Rats.
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使用 ICI 182,780 阻断酒精和雌激素受体对卵巢切除大鼠骨的影响。
DOI：
10.1111/acer.14185
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Turner,RussellT
中科院分区：
文献类型：
--
作者：
Wagner,Lindsay;Howe,Kathy;Philbrick,KennethA;Maddalozzo,GianniF;Kuah,AmidaF;Wong,CarmenP;Olson,DawnA;Branscum,AdamJ;Iwaniec,UrszulaT;Turner,RussellT
背景雌激素信号对骨骼的性别二型性是必不可少的，是成人正常的骨重建平衡所必需的，并可能影响骨骼对酒精的反应。高酒精摄入量降低了卵巢完整但不去卵巢(OVX)大鼠的骨量。然而，OVX后即刻极快的骨丢失速度可能会掩盖酒精的影响。因此，我们确定了(I)重度酒精摄入(35%卡路里摄入量)是否影响已建立松质骨量减少的性成熟OVX大鼠的骨，以及(Ii)强有力的雌激素受体信号拮抗剂ICI182,780(ICI)是否改变了对酒精的骨骼反应。方法OVX三周后，大鼠随机分为5组，(I)基线，(Ii)对照组+ICI，(Iii)对照组+ICI，(Iv)乙醇+ICI，或(V)EtoH+ICI，并相应治疗4周。采用双能X线骨密度仪、计算机断层扫描、血液骨转换指标、股骨和子宫基因表达等方法评价酒精和脑缺血的反应。结果饮酒大鼠骨量减少，脂肪含量增加。胫骨的微结构和股骨的基因表达发生了改变；具体地说，皮质骨的积累减少，松质骨的净丢失，以及与骨转换相关的19/84个基因的差异表达。此外，骨钙素，骨转换的标志，在酒精喂养的大鼠中更低。ICI对体重增加、身体成分或皮质骨没有影响。ICI减少松质骨丢失和血清CTX-1，CTX-1是骨吸收的生化标志物；酒精拮抗后两种反应。酒精和ICI均不影响子宫重量或基因表达。结论无论有无雌激素受体阻滞剂ICI，酒精均可加重去卵巢大鼠的骨丢失。在酒精喂养的OVX大鼠中，酒精对子宫的影响可以忽略不计，而ICI对骨骼的影响有限，这表明在慢性酒精滥用大鼠模型中，雌激素受体信号在酒精对骨骼的作用中发挥的作用有限。
BackgroundEstrogen signaling is essential for the sexual dimorphism of the skeleton, is required for normal bone remodeling balance in adults, and may influence the skeletal response to alcohol. High levels of alcohol consumption lower bone mass in ovary‐intact but not ovariectomized (ovx) rats. However, the extremely rapid rate of bone loss immediately following ovx may obscure the effects of alcohol. We therefore determined (i) whether heavy alcohol consumption (35% caloric intake) influences bone in sexually mature ovx rats with established cancellous osteopenia and (ii) whether ICI 182,780 (ICI), a potent estrogen receptor signaling antagonist, alters the skeletal response to alcohol.MethodsThree weeks following ovx, rats were randomized into 5 groups, (i) baseline, (ii) control + vehicle, (iii) control + ICI, (iv) ethanol (EtOH) + vehicle, or (v) EtOH + ICI, and treated accordingly for 4 weeks. Dual‐energy X‐ray absorptiometry, microcomputed tomography, blood measurements of markers of bone turnover, and gene expression in femur and uterus were used to evaluate response to alcohol and ICI.ResultsRats consuming alcohol had lower bone mass and increased fat mass. Bone microarchitecture of the tibia and gene expression in femur were altered; specifically, there was reduced accrual of cortical bone, net loss of cancellous bone, and differential expression of 19/84 genes related to bone turnover. Furthermore, osteocalcin, a marker of bone turnover, was lower in alcohol‐fed rats. ICI had no effect on weight gain, body composition, or cortical bone. ICI reduced cancellous bone loss and serum CTX‐1, a biochemical marker of bone resorption; alcohol antagonized the latter 2 responses. Neither alcohol nor ICI affected uterine weight or gene expression.ConclusionsAlcohol exaggerated bone loss in ovx rats in the presence or absence of estrogen receptor blockade with ICI. The negligible effect of alcohol on uterus and limited effects of ICI on bone in alcohol‐fed ovx rats suggest that estrogen receptor signaling plays a limited role in the action of alcohol on bone in a rat model for chronic alcohol abuse.
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DOI：
10.1111/j.1530-0277.1997.tb03780.x
发表时间：
1997
期刊：
Alcoholism, clinical and experimental research
影响因子：
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作者：
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通讯作者：
R. Kimble
影响因子：
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作者：
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通讯作者：
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DOI：
10.1111/acer.13000
发表时间：
2016-04
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Gaddini GW;Turner RT;Grant KA;Iwaniec UT
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Iwaniec UT
长期饮酒会导致大鼠维生素 D 代谢紊乱和骨骼异常。
DOI：
10.1111/j.1530-0277.1988.tb00152.x
发表时间：
1988
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Turner,RT;Aloia,RC;Segel,LD;Hannon,KS;Bell,NH
通讯作者：
Bell,NH
影响因子：
4.8
作者：
Kennedy, AM;Shogren, KL;Maran, A
通讯作者：
Maran, A