Insulin- and thyroid hormone-independent adaptation of myofibrillar proteolysis to glucocorticoids.
Myofibrillar protein breakdown in skeletal muscle progresses through two distinct phases in response to chronic glucocorticoid administration in the rat, i.e., an early phase lasting 4-5 days, during which proteolysis increases followed by a later phase during which proteolysis decreases. The possible involvement of insulin and the iodothyronines in this phenomenon has now been examined. Diabetic, thyroidectomized, and normal rats were treated with corticosteroid for 10-11 days, and at timed intervals muscle proteolysis was evaluated by measuring the release of 3-methyl-L-histidine (3-MH) and tyrosine from the perfused hindquarter as well as the excretion of 3-MH in the urine. Corticosterone (CTC) administration to normal rats increased plasma insulin, whereas plasma 3,5,3'-triiodothyronine responded with an early rise followed by a fall after 4-5 days. However, the biphasic response of myofibrillar proteolysis to chronic glucocorticoid treatment was not abolished in CTC-treated diabetic or thyroidectomized rats. CTC treatment increased release of tyrosine by perfused muscle of diabetic rats but, unlike 3-MH release, did not diminish later. Thus the adaptation of myofibrillar proteolysis to chronic glucocorticoid treatment appears to be independent of insulin and thyroid hormones. However, insulin may play a role in curtailing glucocorticoid-induced breakdown of nonmyofibrillar proteins.
Kayali
A G
AG
Clinical Research Center, Massachusetts Institute of Technology, Cambridge 02139.
Goodman
M N
MN
Lin
J
J
Young
V R
VR
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009210:Myofibrils / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013965:Thyroidectomy; D014443:Tyrosine / Q000378:metabolism
D008762:Methylhistidines; D009124:Muscle Proteins; D014443:Tyrosine; C028118:3-methylhistidine; D003345:Corticosterone