Sensitivity of myofibrillar proteins to glucocorticoid-induced muscle proteolysis.
Previous studies have reported that prolonged administration of pharmacological doses of glucocorticoids in young rats results in a rise in urinary 3-methyl-L-histidine (3-MH) excretion followed by a fall to initial levels by 8 days. To determine whether this response reflects events in skeletal muscle, protein breakdown in this tissue was evaluated using the perfused hindquarter preparation with rats treated with corticosterone (10 mg X 100 g-1 X day-1) for 2, 4, or 8 days. Myofibrillar and total cell proteolysis were evaluated by measuring the release of 3-MH and tyrosine, respectively, after inhibition of protein synthesis with cycloheximide. Corticosterone treatment resulted in an early increase (1-4 days) followed by a fall (4-8 days) in 3-MH excretion. 3-MH release by the perfused hindquarter of treated rats responded in a similar manner, in that its release increased at days 2 and 4 and decreased to control levels by day 8. On the other hand, corticosterone treatment did not affect the release of tyrosine by the perfused hindquarter. Corticosterone treatment diminished protein synthesis in muscle by 30-50% (P less than 0.01), which unlike 3-MH release by perfused muscle persisted throughout the treatment period. The data indicate that glucocorticoids specifically augment the breakdown of myofibrillar proteins in skeletal muscle. This response is attenuated with prolonged treatment and is unrelated to a loss of metabolic effectiveness of the steroid. Also our findings suggest that the breakdown of myofibrillar and nonmyofibrillar proteins might be regulated independently.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D008297:Male; D008762:Methylhistidines / Q000652:urine; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009132:Muscles / Q000033:anatomy & histology / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism*; D009929:Organ Size; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D008762:Methylhistidines; D009124:Muscle Proteins; D014443:Tyrosine; C028118:3-methylhistidine