Muscle Fiber Conduction Slowing and Decreased Levels of Circulating Muscle Proteins after Short-Term Dexamethasone Administration in Healthy Subjects

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 4; pp. 1663 - 1671
• Main Authors: Minetto, Marco A., Botter, Alberto, Lanfranco, Fabio, Baldi, Matteo, Ghigo, Ezio, Arvat, Emanuela
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.04.2010
• Subjects: Adult; Anti-Inflammatory Agents - pharmacology; Body Temperature - physiology; Computer Simulation; Creatine; Creatine kinase; Creatine Kinase - blood; Dexamethasone; Dexamethasone - pharmacology; Elbow; Electromyography; Excitability; Glucocorticoids; Humans; Kinases; Knee; Male; Muscle contraction; Muscle Contraction - physiology; Muscle Fatigue - drug effects; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Proteins - metabolism; Muscle Strength - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Myoglobin - metabolism; Myoglobins; Myopathy; Placebos; Protein biosynthesis; Protein structure; Sampling; Sarcolemma - metabolism; Single-Blind Method; Skeletal muscle; Structure-function relationships; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2009-2161

Context: Glucocorticoids are known to decrease protein synthesis and impair membrane excitability of muscle fibers. However, their short-term effects on muscle structure and function of healthy subjects remain poorly understood. Objective: Our objective was to investigate whether steroid administration could decrease the circulating levels of muscle proteins and modify myoelectric indexes of sarcolemmal excitability and fatigability. Design: We conducted a single-blind, placebo-controlled study in 20 men randomized to receive dexamethasone (8 mg/d) or placebo for 1 wk. Blood sampling, force measurements for knee extensors and elbow flexors, and electrophysiological tests for biceps brachii, vastus lateralis and medialis, and tibialis anterior muscles were performed before and after the intervention. Results: Dexamethasone administration improved force by 6.0 ± 6.0% (P = 0.01) for elbow flexors and by 8.5 ± 5.5% (P < 0.01) for knee extensors, decreased levels of creatine kinase by 50.5 ± 30.0% (P < 0.01) and myoglobin by 41.8 ± 17.5% (P < 0.01), and impaired sarcolemmal excitability, as shown by the decline of muscle fiber conduction velocity for the four muscles (range from −6 to −10.5%, P < 0.05). Moreover, significant reductions of the myoelectric manifestations of fatigue were observed for the four muscles; the decrease in the rate of change of the mean frequency of the electromyographic power spectrum ranged from −22.6 to −43.9% (P < 0.05). In contrast, no significant changes were observed in muscle excitability and fatigability in subjects who received the placebo. Conclusions: The demonstration that glucocorticoid-induced muscle impairments can be unraveled by means of blood sampling and noninvasive electrophysiological tests has clinical implications for the early identification of subclinical or preclinical forms of myopathy in treated patients.Short-term glucocorticoid administration decreases muscle protein synthesis and reduces sarcolemmal excitability and myoelectric manifestations of fatigue in healthy subjects.