Regulation of beta myosin heavy chain, c-myc and c-fos proto-oncogenes in thyroid hormone-induced hypertrophy of the rat myocardium.
1. In order to investigate the molecular mechanisms determining the hypertrophic response of the ventricular myocardium to thyroid hormone administration, changes in left and right ventricular expression of the c-myc, c-fos and H-ras proto-oncogenes in response to treatment with 3,3',5-tri-iodothyronine were defined. 2. Adult female Wistar rats were treated with daily subcutaneous injections of 3,3',5-tri-iodothyronine (50 micrograms) for 1, 3, 7 or 14 days (n = 6 in each treatment group) and the results from 3,3',5-tri-iodothyronine-treated animals were compared with those obtained from untreated controls (n = 6). Changes in the weight of the left and right ventricles in response to 3,3',5-tri-iodothyronine treatment were measured; changes in expression of the c-myc, c-fos and H-ras proto-oncogenes were determined in parallel by measurement of specific messenger RNAs by Northern and dot hybridization, as well as changes in expression of beta myosin heavy chain messenger RNA. 3. Treatment with 3,3',5-tri-iodothyronine resulted in increases in both left and right ventricular weights after 3 days, an effect maintained up to 14 days. Despite an increase in left ventricular weight, levels of beta myosin heavy chain, c-myc, c-fos and H-ras mRNAs in the left ventricle were unchanged; in contrast, an increase in right ventricular weight was associated with increased expression of beta myosin heavy chain, c-myc and c-fos messenger RNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
Green
N K
NK
Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, U.K.
Gammage
M D
MD
Franklyn
J A
JA
Heagerty
A M
AM
Sheppard
M C
MC
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D006332:Cardiomegaly / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000502:physiology*; D016259:Genes, myc / Q000502:physiology*; D006321:Heart / Q000187:drug effects*; D015151:Immunoblotting; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000096:biosynthesis / Q000235:genetics*; D010770:Phosphotransferases / Q000235:genetics; D015800:Protozoan Proteins; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology*
D015800:Protozoan Proteins; D014284:Triiodothyronine; D010770:Phosphotransferases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C033142:myosin-heavy-chain kinase; D009218:Myosins