Pharmacological inhibition of TRalpha1 receptor potentiates the thyroxine effect on body weight reduction in rats: potential therapeutic implications in controlling body weight.

It has been previously reported that thyroid hormone receptor alpha1 (TRalpha1) is involved in the regulation of food intake and heart rhythm. Herein, we show that pharmacological inhibition of TRalpha1 by dronedarone, an amiodarone like compound (shown to antagonize thyroid hormone binding to TRalpha1), prevented the thyroid hormone induced increase in food intake and heart rate acceleration in rats. This resulted in a marked reduction in body weight. It is likely that thyroid analogs may prove potential therapeutic agents for controlling body weight.

Blockade of angiotensin II type 1 receptor diminishes cardiac hypertrophy, but does not abolish thyroxin-induced preconditioning.

Growth and stress seem to share common intracellular pathways and activation of growth signaling can increase resistance to stress. Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against ischemia reperfusion injury. The present study investigated whether this response is mediated by renin-angiotensin system (RAS). RAS is shown to be activated in hyperthyroidism and is involved in the development of cardiac hypertrophy. Male Wistar rats were treated with L-thyroxin (25 microg/100 g, sc, od) for fourteen days, while normal rats served as controls. In addition, irbesartan (150 mg/kg po), a potent blocker of angiotensin II type 1 receptor (AT1), was given with L-thyroxin for fourteen days. Isolated hearts were perfused in Langendorff mode; after stabilization, they were subjected to 20 min zero-flow global ischemia and 45 min of reperfusion. Thyroxin induced cardiac hypertrophy, which was diminished with irbesartan administration. Post-ischemic recovery of function was increased in thyroxin-treated hearts as compared to controls while ischemic contracture was accelerated and intensified. Irbesartan did not abolish this response. In conclusion, blockade of angiotensin II type 1 receptor with irbesartan preserves thyroxin-induced cardioprotection while diminishing cardiac hypertrophy. It is likely that thyroxin-induced cardioprotection is due to a direct effect of thyroid hormone.