Alpha and beta glucocorticoid receptor mRNA expression in skeletal muscle.
The aim of the present study was to investigate the occurrence and autoregulation of both glucocorticoid receptor mRNAs in rat gastrocnemius muscle. The expression of both receptor forms was studied 1, 4 or 12 hours after intra-tracheal instillation of a high dose (100 micrograms) of budesonide; muscular expression was compared with glucocorticoid receptor expression in lung tissue. After Northern blot analysis, hybridization was performed with glucocorticoid receptor, glyceraldehyde-3-phosphate dehydrogenase and glutamine synthetase probes. In the gastrocnemius muscle, both the alpha and beta glucocorticoid receptor mRNA forms were detected and found to be downregulated four hours after the budesonide instillation. alpha/beta glucocorticoid receptor ratios were lower in the gastrocnemius (1.1 +/- 0.2) than in the lungs (2.6 +/- 0.6). In the lungs, at all time points, the average alpha glucocorticoid receptor mRNA levels did not differ from controls, although glutamine synthetase mRNA levels were upregulated. The beta glucocorticoid receptor mRNA was slightly reduced at 1 and 4 hours. In conclusion, after intra-tracheal instillation of budesonide, both alpha and beta glucocorticoid receptor forms were downregulated in muscle tissue. The difference in alpha/beta glucocorticoid receptor mRNA ratios and concentrations between lung and gastrocnemius muscle supports the hypothesis of differential gene regulation by glucocorticoids in different cell types.
Korn
S H
SH
Department of Pulmonology, Maastricht University, The Netherlands.
Koerts-de Lang
E
E
Engel
G E
GE
Arends
J W
JW
Wouters
E F
EF
Thunnissen
F B
FB
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*
D000336:Aerosols; D009124:Muscle Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D019819:Budesonide