Influence of clofibrate on thyroid hormone and muscle protein turnover.
Clofibrate, a hypolipidemic agent, has been shown to increase muscle protein degradation. The possible role of thyroid hormones in this phenomena was examined. Clofibrate treatment of rats for 2 weeks resulted in a significant decrease in total thyroxine and triiodothyronine levels in serum. Reverse T3 and resin uptake values remained unchanged. When exogenous thyroxine was co-administered with clofibrate, serum TSH levels were suppressed, but the increased muscle protein degradation was not reversed. Equilibrium dialysis and Scatchard analysis of the binding of 125I-thyroxine to serum proteins indicated that clofibrate competitively inhibits the binding of thyroid hormone to serum proteins by decreasing its apparent binding affinity. In the presence of lower total thyroid hormone concentrations and an elevated free thyroxine fraction, the total free hormone levels are estimated to be in the normal range in the serum of clofibrate treated rats. Clofibrate seems to act like thyroid hormone since it binds to and displaces T4 from plasma proteins. Because free thyroid hormone levels are in the normal range, the thyroid hormone-like effects of clofibrate on the cell may be additive to the T4 effects, and are probably responsible for the hypermetabolic state seen in the muscle of clofibrate-treated animals. Our data suggest that the effects of clofibrate in muscle are complex. In addition to competitively altering the binding of thyroxine to serum proteins, this substance may also exert a hitherto unrecognized thyroid-hormone-like subcellular effect resulting in increased muscle protein degradation, and in augmented ouabain-sensitive ATPase activities.
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000097:blood*; D013975:Thyroxine-Binding Proteins / Q000378:metabolism
D009124:Muscle Proteins; D013963:Thyroid Hormones; D013975:Thyroxine-Binding Proteins; D002994:Clofibrate