Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms [ChIP-seq]

Glucocorticoid steroids are commonly prescribed for inflammatory conditions such as rheumatoid arthritis and acute respiratory distress, but chronic daily use produces an array of adverse effects including muscle wasting and weakness. In contrast, shorter and lower dose glucocorticoid pulses may improve athletic performance, although the mechanisms by which this occurs remain unclear. Muscle is sexually dimorphic and comparatively little is known about how male and female muscle respond to glucocorticoid steroids. In this work, we investigated the impact of a once-weekly glucocorticoid exposure on body mass and skeletal muscle performance, comparing male and female mice. We performed RNA sequencing of isolated myofibers from quadriceps of C57BL/6 male and female mice given vehicle, weekly, or daily prednisone for one month. Overall design: H3K27ac ChIP sequencing of one control (vehicle) and three treatment (four, six, and eight days after fifth injection of weekly prednisone) groups, n=2 males and 2 females per treatment

糖皮质激素（glucocorticoid steroids）常被用于治疗类风湿关节炎、急性呼吸窘迫等炎症性疾病，但长期每日给药会引发一系列不良反应，包括肌肉萎缩与肌力减退。与之相反，短疗程、低剂量的糖皮质激素冲击疗法或许可提升运动表现，但其背后的作用机制目前仍不明确。肌肉组织存在性二态性，目前关于雌雄个体的肌肉对糖皮质激素的应答机制仍知之甚少。本研究以C57BL/6品系雌雄小鼠为研究对象，探究了每周一次的糖皮质激素暴露对体质量与骨骼肌功能的影响。我们对接受溶剂对照、每周一次或每日泼尼松（prednisone）给药、持续1个月的C57BL/6雌雄小鼠的股四头肌分离肌纤维进行了RNA测序（RNA sequencing）。实验整体设计：对1个对照组（溶剂对照）与3个给药组（分别为每周泼尼松第5次给药后的第4、6、8天）进行H3K27乙酰化染色质免疫共沉淀测序（ChIP sequencing），每组雌雄小鼠各2只。