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.