Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle group specific mechanisms in humans.
Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content, maximal activity and subunit specific mRNA level (alpha1, alpha2, beta1, beta2, beta3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as alpha1, alpha2, beta1 and beta2 mRNA levels were higher (P < 0.05) in vastus lateralis than in deltoid. Dexamethasone treatment increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 +/- 7% (P < 0.05) and 18 +/- 6% (P < 0.05) as well as Na+,K+ pump content by 18 +/- 9% (P < 0.001) and 24 +/- 8% (P < 0.01), respectively. Treatment with dexamethasone resulted in a higher alpha1, alpha2, beta1 and beta2 mRNA expression in the deltoid (P < 0.05), but no effects on Na+,K+ pump mRNA were detected in vastus lateralis. In conclusion, dexamethasone treatment increased maximal Na+,K+ pump activity in both vastus lateralis and deltoid muscles. The relative importance of transcription and translation in the glucocorticoid-induced regulation of Na+,K+ pump expression seems to be muscle specific and possibly dependent on the actual training condition of the muscle, such that a high Na+,K+ pump maximal activity and mRNA level prior to treatment prevents the transcriptional response to dexamethasone, but not the increase in Na+,K+ pump content and maximal activity.
August Krogh Institute, Institute of Exercise and Sport Sciences, Universitetsparken 13, 2. floor, 2100 Copenhagen, Denmark.
Nikolai
N
Nordsborg
Craig
C
Goodmann
Michael J
MJ
McKenna
Jens
J
Bangsbo
D000284:Administration, Oral; D000328:Adult; D003907:Dexamethasone / Q000008:administration & dosage*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014018:Tissue Distribution; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase