Document Detail


Influence of clofibrate on thyroid hormone and muscle protein turnover.
MedLine Citation:
PMID:  6436638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D C Lehotay; H S Paul; S A Adibi; G S Levey
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  33     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  1984 Nov 
Date Detail:
Created Date:  1984-12-03     Completed Date:  1984-12-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1048-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Clofibrate / pharmacology*
Male
Muscle Proteins / metabolism*
Protein Binding
Rats
Rats, Inbred Strains
Thyroid Hormones / blood*
Thyroxine-Binding Proteins / metabolism
Grant Support
ID/Acronym/Agency:
AM15855/AM/NIADDK NIH HHS; HL12715/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Muscle Proteins; 0/Thyroid Hormones; 0/Thyroxine-Binding Proteins; 637-07-0/Clofibrate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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