The Influence of Glucocorticoid Receptor on Sex Differences of Gene Expression Profile in Skeletal Muscle
The Influence of Glucocorticoid Receptor on Sex Differences of Gene Expression Profile in Skeletal Muscle
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糖皮质激素受体对骨骼肌基因表达谱性别差异的影响
DOI：
10.1080/07435800.2021.1884874
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发表时间：
2021
影响因子：
2.1
通讯作者：
Tanaka Hirotoshi
中科院分区：
文献类型：
--
作者：
Yoshikawa Noritada;Oda Aya;Yamazaki Hiroki;Yamamoto Motohisa;Kuribara-Souta Akiko;Uehara Masaaki;Tanaka Hirotoshi
骨骼肌作为运动系统发挥作用，并维持全身代谢。这种骨骼肌形态和功能的性别差异已被证明，然而，其潜在的机制仍然难以捉摸。糖皮质激素是维持体内平衡的肾上腺皮质激素，除了调节应激反应外，还包括调节全身能量代谢。在骨骼肌中，糖皮质激素可通过转录因子糖皮质激素受体（GR）减少肌肉蛋白质的合成，同时加速蛋白质的分解，从而调节骨骼肌的质量和能量代谢。我们在此评估了GR的相关贡献，性别差异的基因表达谱在骨骼肌GR-floxed（GRF/F）和骨骼肌特异性GR敲除（GRmKO）小鼠。腓肠肌GR mRNA和蛋白表达水平在雌雄间无差异。使用GRF/f和GRmKO小鼠的腓肠肌进行的DNA微阵列分析显示，尽管大多数基因表达水平在两种性别中相同，但与胆固醇和载脂蛋白合成以及脂肪酸生物合成和免疫系统相关的基因主要在雄性和雌性中表达。分别在GRF/f中，而不是在GRmKO小鼠中。此外，许多基因在GRf/f中响应于饥饿而上调，但在GRmKO小鼠中则没有，其中许多基因是性别无关的，并且具有维持稳态的功能，而表现出性别优势的基因与多种功能相关。虽然骨骼肌中表达的基因可能主要是性别无关的，但性别显性基因可能与能量代谢和免疫系统的性别差异有关，并可能受到GR的控制。
Skeletal muscle functions as a locomotory system and maintains whole-body metabolism. Sex differences in such skeletal muscle morphology and function have been documented; however, their underlying mechanisms remain elusive. Glucocorticoids are adrenocortical hormones maintaining homeostasis, including regulating whole-body energy metabolism in addition to stress response. In skeletal muscle, glucocorticoids can reduce the synthesis of muscle proteins and simultaneously accelerate the breakdown of proteins to regulate skeletal muscle mass and energy metabolism via a transcription factor glucocorticoid receptor (GR). We herein evaluated the related contributions of the GR to sex differences of gene expression profiles in skeletal muscle using GR-floxed (GRf/f) and skeletal muscle-specific GR knockout (GRmKO) mice. There were no differences in GR mRNA and protein expression levels in gastrocnemius muscle between males and females. A DNA microarray analysis using gastrocnemius muscle from GRf/f and GRmKO mice revealed that, although most gene expression levels were identical in both sexes, genes related to cholesterol and apolipoprotein synthesis and fatty acid biosynthesis and the immunological system were predominantly expressed in males and females, respectively, in GRf/f but not in GRmKO mice. Moreover, many genes were up-regulated in response to starvation in GRf/f but not in GRmKO mice, many of which were sex-independent and functioned to maintain homeostasis, while genes that showed sex dominance related to a variety of functions. Although the genes expressed in skeletal muscle may be predominantly sex-independent, sex-dominant genes may relate to sex differences in energy metabolism and the immune system and could be controlled by the GR.