Oxidative stress activates insulin-like growth factor I receptor protein expression, mediating cardiac hypertrophy induced by thyroxine.

Thyroxine can cause cardiac hypertrophy by activating growth factors, such as IGF-I (insulin-like growth factor-I). Since oxidative stress is enhanced in the hyperthyroidism, it would control protein expression involved in this hypertrophy. Male Wistar rats were divided into four groups: (I) control, (II) vitamin E-supplemented (20 mg/kg/day subcutaneous), (III) hyperthyroid (thyroxine 12 mg/l, in drinking water), and (IV) hyperthyroid + vitamin E. After 4 weeks, the contractility and relaxation indexes of left ventricle (LV), and cardiac mass were increased by 54%, 60%, and 60%, respectively, in hyperthyroid group. An increase in lipid peroxidation (around 40%), and a decrease in total glutathione (by 20%) was induced by thyroxine and avoided by vitamin E administration. Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were increased (by 83% and 54%, respectively) in hyperthyroid, and vitamin E avoided changes in SOD. Protein expression of SOD, GST, and IGF-I receptor (IGF-IR) were increased (by 87%, 84%, and 60%, respectively) by thyroxine, and vitamin E promoted a significant reduction in SOD and IGF-IR expression (by 36% and 17%, respectively). These results indicate that oxidative stress is involved in cardiac hypertrophy, and suggest a role for IGF-IR as a mediator of this adaptive response in experimental hyperthyroidism.