Thyroid hormone effects on cardiac gene expression independent of cardiac growth and protein synthesis.
Prior studies have demonstrated the importance of hemodynamic loading in mediating thyroxine (T4)-induced cardiac hypertrophy. Direct cellular effects of thyroid hormone have been implicated in modulating the expression of the myosin heavy chain (MHC) genes and the slow sarcoplasmic reticulum calcium adenosine triphosphatase (SR Ca(2+)-ATPase) gene. In the present report, administration of T4 for 72 h did not stimulate growth of the hemodynamically unloaded heterotopic isograft. The synthetic rates of total cardiac proteins and MHC in the isograft remained significantly lower at 64 and 53% of the respective rates measured simultaneously in the in situ working heart. Although total left ventricle RNA content in the isograft was unchanged by T4, alpha-MHC and SR Ca(2+)-ATPase mRNA concentrations were increased 181 and 208%, respectively, and the previously observed beta-MHC expression was completely prevented. These data indicate that, although T4 requires an increased hemodynamic load to stimulate cardiac protein synthesis, it is capable of directly altering the expression of at least two myocyte-specific genes. Therefore some of the phenotypic alterations observed with thyroid hormone treatment are the result of direct effects of the hormones on specific cardiac genes and independent of changes in cardiac growth.
Ojamaa
K
K
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
Samarel
A M
AM
Kupfer
J M
JM
Hong
C
C
Klein
I
I
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006321:Heart / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology*; D016027:Heart Transplantation; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis / Q000235:genetics; D009696:Nucleic Acids / Q000378:metabolism; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013963:Thyroid Hormones / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D009124:Muscle Proteins; D009696:Nucleic Acids; D012333:RNA, Messenger; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I; D009218:Myosins; D000252:Calcium-Transporting ATPases