L-Thyroxine activates Akt signaling in the heart.
Hyperthyroidism causes physiological cardiac hypertrophy and enhanced function. Many of these effects have been traditionally attributed to changes in gene expression. However, the role of signal transduction pathways in the effects mediated by thyroid hormone (TH) have recently gained a significant amount of attention in non-cardiovascular cells and tissue. Whether signal transduction pathways are involved in the cardiac effects of TH is unknown. In this study, we treated Sprague Dawley rats with L-thyroxine (T4) or propylthiouracil (PTU) to determine whether there was modulation of signal transduction pathways in the left ventricle. Predictably, T4 increased heart weight, left ventricular systolic pressure, and dP/dT. T4 and PTU also had typical effects on expression of thyroid responsive genes such as alpha and beta myosin heavy chain. T4 treatment caused phosphorylation of Akt and downstream signaling components such as GSK-3beta, mTOR, and S6 kinase. In conclusion, activation of the Akt signaling pathway may contribute to the effects of TH on the heart. While this pathway is clearly activated, further work is needed to determine whether this is via a genomic or non-genomic mechanism.
Kuzman
James A
JA
School of Medicine, University of South Dakota, Cardiovascular Research Institute-South Dakota Health Research Foundation, 1100 East 21st Street, Sioux Falls, SD 57105, USA.
Vogelsang
Kathryn A
KA
Thomas
Tracy A
TA
Gerdes
A Martin
AM
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013974:Thyroxine / Q000494:pharmacology*
D003285:Contractile Proteins; D011441:Propylthiouracil; D051057:Proto-Oncogene Proteins c-akt; D013974:Thyroxine