Glucocorticoids do not regulate the expression of proteolytic genes in skeletal muscle from Cushing's syndrome patients.
Glucocorticoids signal enhanced proteolysis in various instances of muscle atrophy and increased gene expression of components of the lysosomal, Ca(2+)-dependent, and/or ubiquitin-proteasome proteolytic pathways in both rat skeletal muscle and myotubes. Cushing's syndrome is characterized by chronic excessive glucocorticoid production, which results in muscle wasting. We report here no change in messenger RNA levels for cathepsin D (a lysosomal proteinase), m-calpain (a Ca(2+)-activated proteinase), ubiquitin, 14-kDa ubiquitin-activating enzyme E2, and 20S proteasome subunits (i.e. critical components of the ubiquitin-proteasome proteolytic process) in skeletal muscle from such patients. Thus, in striking contrast with animal studies, glucocorticoids did not regulate the expression of muscle proteolytic genes in Cushing's syndrome. In humans, messenger RNA levels, for at least ubiquitin and proteasome subunits, are elevated in acute situations of muscle wasting, such as head trauma or sepsis. Because Cushing's syndrome is a chronic catabolic condition, we suggest that the lack of regulation of proteolytic genes in such patients may represent an adaptive regulatory mechanisms, preventing sustained increased protein breakdown and avoiding rapid muscle wasting.
Rallière
C
C
Institut Natíonal de Recherche Agronomique, Unité d'Etude du Métabolisme Azoté, Ceyrat, France.
Tauveron
I
I
Taillandier
D
D
Guy
L
L
Boiteux
J P
JP
Giraud
B
B
Attaix
D
D
Thiéblot
P
P
D000328:Adult; D002154:Calpain / Q000235:genetics; D002402:Cathepsin D / Q000235:genetics; D003480:Cushing Syndrome / Q000235:genetics* / Q000503:physiopathology*; D003546:Cysteine Endopeptidases / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010447:Peptide Hydrolases / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics
D005938:Glucocorticoids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014452:Ubiquitins; D010447:Peptide Hydrolases; D002154:Calpain; D003546:Cysteine Endopeptidases; D002402:Cathepsin D; D046988:Proteasome Endopeptidase Complex