Hormonal regulation of myosin heavy chain and alpha-actin gene expression in cultured fetal rat heart myocytes.
Thyroid hormone regulates the expression of ventricular myosin isoenzymes by causing an accumulation of alpha-myosin heavy chain (MHC) mRNA and inhibiting expression of beta-MHC mRNA. However, the mechanism of thyroid hormone action has been difficult to examine in vivo because of its diverse actions. Accordingly, hormonal control of expression of six MHC isoform mRNAs and cardiac and skeletal alpha-actin mRNAs was studied in primary cultures of fetal rat heart myocytes grown in defined medium. The results indicate that in the absence of thyroid hormone, cultured heart cells express predominantly beta-MHC and cardiac alpha-actin mRNAs. Addition of 3,5,3'-triiodo-L-thyronine (T3) caused a rapid induction of alpha-MHC mRNA and decreased beta-MHC mRNA levels without affecting the skeletal muscle MHC mRNAs. There was an almost parallel change in the myosin isoenzymes. Cardiac alpha-actin mRNA levels were transiently increased by T3 treatment, but skeletal alpha-actin was unaffected. Elimination of insulin and epithelial growth factor from the medium did not alter the effects of T3 on cardiac MHC mRNA expression. Addition of various adrenergic agents to the medium had no appreciable effect on cardiac MHC mRNA expression despite the presence of functionally coupled alpha- and beta-adrenergic receptors. Addition of steroid hormones, muscarinic agents, and glucagon to the medium also had no effect. Thus, under defined conditions, T3 is able to regulate MHC gene expression at a pretranslational level without the need for other exogenous factors.
D000199:Actins / Q000235:genetics*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005796:Genes / Q000187:drug effects*; D006321:Heart / Q000196:embryology; D006728:Hormones / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D015879:Myosin Subfragments; D009218:Myosins / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014284:Triiodothyronine / Q000494:pharmacology*
D000199:Actins; D006728:Hormones; D015879:Myosin Subfragments; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D014284:Triiodothyronine; D003994:Bucladesine; D009218:Myosins