Effects of high doses of glucocorticoids on free amino acids, ribosomes and protein turnover in human muscle.
BACKGROUND
Treatment with glucocorticosteroids causes a negative nitrogen balance, but the kinetic mechanisms responsible for this catabolic effect are controversial. We investigated the effects of 60 mg day(-1) prednisolone on protein synthesis and degradation in human skeletal muscle.


METHODS
Healthy adults (n = 9) were studied in the postabsorptive state, before and after 3 days of prednisolone treatment. The L-[ring 2,6(-3)H(5)]-phenylalanine tracer technique, concentration and size distribution of the ribosomes, mRNA content of the ubiquitin-proteasome pathway components in muscle, phenylalanine flux across the leg, and the free amino acid concentrations in skeletal muscle were used to study muscle protein metabolism.


RESULTS
The concentrations of most amino acids in arterial blood increased after prednisolone. There were also increased effluxes of phenylalanine, asparagine, arginine, alanine, methionine and isoleucine from the leg. The rate of protein degradation, as measured by the appearance rate (Ra) of phenylalanine, increased by 67% (P = 0.023) which, together with a doubling of the net release of phenylalanine from the leg (P = 0.007), indicated accelerated protein degradation. The pathway was not identified but there was no significant increase in mRNAs' encoding components of the ubiquitin-proteasome pathway. There was a 6% reduction in polyribosomes (P = 0.007), suggesting a decrease in the capacity for protein synthesis, although there was no measured decrease in the rate of protein synthesis.


CONCLUSIONS
These findings indicate that high doses of prednisolone lead to a sharp increase in net protein catabolism, which depends more on enhanced protein breakdown, and an uncertain effect on protein synthesis. The mechanisms stimulating proteolysis and the pathway stimulated to increase muscle protein degradation should be explored.
Löfberg
E
E
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. erland.lofberg@klinvet.ki.se
Gutierrez
A
A
Wernerman
J
J
Anderstam
B
B
Mitch
W E
WE
Price
S R
SR
Bergström
J
J
Alvestrand
A
A
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007866:Leg; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism*; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
D000596:Amino Acids; D005938:Glucocorticoids; D009124:Muscle Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; D010649:Phenylalanine; D011239:Prednisolone