Thyroid hormone action in the heart

The heart is a major target organ for thyroid hormone action, and marked changes occur in cardiac function in patients with hypo- or hyperthyroidism. T-3-induced changes in cardiac function can result from direct or indirect T-3 effects. Direct effects result from T-3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T-3 effects, which occur independent of nuclear T-3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T-3 effects are mediated by the binding of T-3 to specific nuclear receptor proteins, which results in increased transcription of T-3-responsive cardiac genes. The T-3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. T-3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum. This T-3 effect results from T-3-induced increases in the level of the mRNA coding for the sarcoplasmic reticulum calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the sarcoplasmic reticulum.