Influence of clofibrate on thyroid hormone and muscle protein turnover.
Influence of clofibrate on thyroid hormone and muscle protein turnover.
复制标题
安妥明对甲状腺激素和肌肉蛋白周转的影响。
DOI：
10.1016/0026-0495(84)90236-1
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Levey,GS
中科院分区：
文献类型：
--
作者：
Lehotay,DC;Paul,HS;Adibi,SA;Levey,GS
氯贝特是一种降血脂药物，已被证明可以增加肌肉蛋白质的降解。研究了甲状腺激素在这一现象中的可能作用。氯贝特治疗2周后，大鼠血清总甲状腺素和三碘甲腺原氨酸水平明显下降。反向T3和树脂吸收值保持不变。当外源性甲状腺激素与氯贝特联合应用时，血清TSH水平被抑制，但增加的肌肉蛋白质降解不能逆转。平衡透析和125I-甲状腺素与血清蛋白结合的Scatchard分析表明，氯贝特通过降低甲状腺激素与血清蛋白的表观结合亲和力而竞争性地抑制其与血清蛋白的结合。在存在较低的总甲状腺激素浓度和较高的游离甲状腺激素组分的情况下，氯贝特治疗的大鼠血清中的总游离激素水平估计在正常范围内。氯贝特的作用似乎类似于甲状腺激素，因为它与血浆蛋白结合并取代T4。由于游离甲状腺激素水平在正常范围内，氯贝特对细胞的甲状腺激素样效应可能是对T4效应的相加，可能是氯贝特治疗动物肌肉中出现的高代谢状态的原因。我们的数据表明，氯贝特对肌肉的影响是复杂的。除了竞争性地改变甲状腺激素与血清蛋白的结合，这种物质还可能发挥迄今未被认识的甲状腺激素样亚细胞效应，导致肌肉蛋白质降解增加，并增强哇巴因敏感的ATPase活性。
Clofibrate, a hypolipidemic agent, has been shown to increase muscle protein degradation. The possible role of thyroid hormones in this phenomena was examined. Clofibrate treatment of rats for 2 weeks resulted in a significant decrease in total thyroxine and triiodothyronine levels in serum. Reverse T3and resin uptake values remained unchanged. When exogenous thyroxine was co-administered with clofibrate, serum TSH levels were suppressed, but the increased muscle protein degradation was not reversed. Equilibrium dialysis and Scatchard analysis of the binding of125I-thyroxine to serum proteins indicated that clofibrate competitively inhibits the binding of thyroid hormone to serum proteins by decreasing its apparent binding affinity. In the presence of lower total thyroid hormone concentrations and an elevated free thyroxine fraction, the total free hormone levels are estimated to be in the normal range in the serum of clofibrate treated rats. Clofibrate seems to act like thyroid hormone since it binds to and displaces T4from plasma proteins. Because free thyroid hormone levels are in the normal range, the thyroid hormone-like effects of clofibrate on the cell may be additive to the T4effects, and are probably responsible for the hypermetabolic state seen in the muscle of clofibrate-treated animals. Our data suggest that the effects of clofibrate in muscle are complex. In addition to competitively altering the binding of thyroxine to serum proteins, this substance may also exert a hitherto unrecognized thyroid-hormone-like subcellular effect resulting in increased muscle protein degradation, and in augmented ouabain-sensitive ATPase activities.