Mitochondrial protein synthesis during thyroxine-induced cardiac hypertrophy

The goal of this paper was to determine the effects of 3,5,3'-triiodothyronine (T₃)-thyroxine-induced cardiac hypertrophy on the rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthesis systems and to compare the results with total protein synthesis and cardiac enlargement. Daily injections of T₃-thyroxine in the rat resulted in a 25% increase in the growth of the ventricle compared with controls. The cytoplasmic synthesis of both mitochondrial and total proteins as measured in the isolated perfused heart was stimulated by T₃-thyroxine injection to a peak of 155 and 146%, respectively, of vehicle-injected controls after 3 days of hormone treatment. This peak was followed by a gradual decline in stimulation in total protein synthesis to 132% of control by 9 days of injection, whereas the decline in stimulation of cytoplasmic synthesis of mitochondrial proteins was significantly steeper, falling to 119% of vehicle control. The rate of protein synthesis within the the mitochondrial compartment was also measured during the time course of T₃-thyroxine-induced hypertrophy. These rates were measured in an isolated intact heart mitochondrial protein synthesis system described and characterized in the companion papers [E.E. McKee, B.L. Grier, G.S. Thompson, and J.D. McCourt. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E492-E502, 1990; and E.E. McKee, B.L. Grier, G.S. Thompson, A.C.F. Leung, and J.D. McCourt. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E503-E510, 1990]. Rates of mitochondrial protein synthesis were dramatically stimulated by T₃-thyroxine injection. A statistically significant increase of 119% of control was observed after only 12 h of treatment, which increased to 198% of control after 3 days of treatment. Interestingly, this stimulation also decreased markedly to 125% of control by 9 days of injection accomapnied by a possible reduction in the rate of elongation. These data clearly demonstrate that the synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthetic systems is stimulated in response to T₃-thyroxine-induced cardiac hypertrophy in a biphasic manner. Furthermore, this stimulation does not follow the same pattern as that of total protein suggesting that synthesis of mitochondrial proteins may be differentially regulated.