Duclos Martine, Gouarne Caroline, Martin Cyril, Rocher Christophe, Mormède Pierre, Letellier Thierry
Laboratoire Neurogénétique et Stress, Institut National de la Santé et de la Recherche Médicale U471, Institut François Magendie, Université Bordeaux II, 33077 Bordeaux, France.
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E159-67. doi: 10.1152/ajpendo.00281.2003. Epub 2003 Sep 9.
Previous studies in rat have demonstrated decreased number of mitochondria and uncoupling of oxidative phosphorylation after administration of glucocorticoids but at supraphysiological doses and using synthetic glucocorticoids. To analyze the relationships between corticosterone levels (the natural glucocorticoid in rat) and muscle mitochondrial metabolism, Lewis and Fischer 344 rats were bilaterally adrenalectomized and implanted with different corticosterone pellets (0, 12, 50, 100, and 200 mg of corticosterone). Rats bearing a corticosterone pellet delivering corticosterone at concentrations in the range of chronic stress-induced levels presented a lower amount of functional muscle mitochondria with a decrease in cytochrome c oxidase and citrate synthase activities and a depletion of mitochondrial DNA. Moreover, a strain difference in tissue sensitivity to corticosterone was depicted both in end-organ sensitive to glucocorticoids (body, thymus, and adrenal weights) and in muscle mitochondrial metabolism (Lewis > Fischer). Interestingly, this strain difference was also observed in the absence of corticosterone, with a deleterious effect on muscle mitochondrial metabolism in Fischer rats, whereas no effects were observed in Lewis rats. We therefore postulate that corticosterone is necessary for muscle mitochondrial metabolism exerting its effects in Fischer rats with an inverted U curve, whereby too little (only Fischer) or too much (Fischer and Lewis) corticosterone is deleterious to muscle mitochondrial metabolism. In conclusion, we propose a general model of coordinate regulation of mitochondrial energetic metabolism by glucocorticoids.
先前在大鼠身上进行的研究表明，给予糖皮质激素后线粒体数量减少且氧化磷酸化解偶联，但使用的是超生理剂量的合成糖皮质激素。为了分析皮质酮水平（大鼠体内的天然糖皮质激素）与肌肉线粒体代谢之间的关系，对刘易斯大鼠和费希尔344大鼠进行双侧肾上腺切除术，并植入不同剂量的皮质酮微丸（0、12、50、100和200毫克皮质酮）。携带皮质酮微丸、皮质酮浓度处于慢性应激诱导水平范围内的大鼠，其功能性肌肉线粒体数量较少，细胞色素c氧化酶和柠檬酸合酶活性降低，线粒体DNA减少。此外，在对糖皮质激素敏感的终末器官（体重、胸腺和肾上腺重量）以及肌肉线粒体代谢方面（刘易斯大鼠>费希尔大鼠），均呈现出对皮质酮的组织敏感性存在品系差异。有趣的是，在没有皮质酮的情况下也观察到了这种品系差异，对费希尔大鼠的肌肉线粒体代谢有有害影响，而在刘易斯大鼠中未观察到影响。因此，我们推测皮质酮对于肌肉线粒体代谢是必需的，在费希尔大鼠中其作用呈倒U形曲线，即皮质酮过少（仅费希尔大鼠）或过多（费希尔大鼠和刘易斯大鼠）均对肌肉线粒体代谢有害。总之，我们提出了一个糖皮质激素对线粒体能量代谢进行协调调节的通用模型。
