Protein synthesis and degradation during regression of thyroxine-induced cardiac hypertrophy.

To characterize changes in rates of protein turnover during regression of thyroxine-induced left ventricular hypertrophy, New Zealand White rabbits received intravenous thyroxine (200 micrograms/kg/d) for 9 days. Thyroxine was withheld, and in vivo protein turnover was evaluated on the 10th, 15th and 20th days. Animals not receiving thyroxine served as controls. Heart rate, blood pressure, and rate-pressure product were measured to correlate changes in cardiac work with protein turnover rates during the development and regression of hypertrophy. Thyroxine administration produced left ventricular hypertrophy by increasing the rate of protein synthesis (from 37.9 +/- 8.9 to 64.1 +/- 15.3 mg/day; P less than 0.05) to a greater degree than protein degradation (from 29.8 +/- 8.9 to 48.2 +/- 15.3 mg/day for control and thyroxine-treated animals, respectively; P less than 0.05). Cessation of thyroxine administration resulted in an eventual return of left ventricular mass to that of normally growing control animals. The major observation noted during thyroxine withdrawal was a return of protein synthetic rates to normal. Absolute rates of protein degradation remained elevated, whereas fractional protein degradative rates (i.e. the fraction of total protein degraded per day) were unchanged by the administration and withdrawal of thyroxine. These results indicate that suppression of both physiological and hormone-induced growth following cessation of thyroxine resulted from a decrease in cardiac protein synthetic rates and an increased rate of flux through the protein degradative pathway(s), while fractional rates of protein degradation (and thus average protein half-life) remained unchanged. The development and regression of thyroxine-induced hypertrophy correlated with thyroxine-mediated alterations in cardiac work.