Acute cellular actions of thyroid hormone and myocardial function.

Abstract

The mechanisms of actions of thyroid hormone in various tissues are largely viewed as cell nucleus-mediated. However, several actions of this hormone are definitively extranuclear, and these include effects on the activities of Ca(2+)-adenosine triphosphatases (ATPases) of myocardial sarcolemma and, apparently, sarcoplasmic reticulum in animal models. Both effects would serve to reduce cytoplasmic (sarcoplasmic) [Ca2+]. Sarcoplasmic reticulum uptake of Ca2+ from sarcoplasm is mediated by Ca(2+)-ATPase and is deficient in end-stage heart failure; thyroid hormone can enhance sarcoplasmic reticulum Ca(2+)-ATPase activity acutely via an extranuclear mechanism or indirectly via the myosin-associated Ca(2+)-ATPase gene. Such actions would serve to improve myocardial relaxation, thus improvement in diastolic dysfunction, and may be cardioprotective if excessive levels of sarcoplasmic [Ca2+] develop during reperfusion of previously ischemic tissue. Action of thyroid hormone on sarcolemmal Ca(2+)-ATPase activity will enhance Ca2+ efflux, and a recently described effect of the hormone on myocardial Na+ inactivation current may serve to increase or reduce sarcoplasmic [Ca2+], depending upon the vector of Na+/Ca2+ exchange. This article reviews acute effects of thyroid hormone on the heart that are extranuclear in mechanism.