Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones.

The effect of thyroid hormone on the expression of ventricular isomyosins V1, V2, and V3 was studied in fetal and neonatal rats. Between 15 and 21 days gestation, V3 accounts for 80-90% of fetal ventricular myosin. After birth, there is a rapid transition from the fetal V3 isotype to an equal mixture of V1 and V3 at 3 days, and to 100% V1 at 3 weeks of age. The endogenous serum levels of thyroxine (T4) and triiodothyronine (T3) increase from trace amounts in the fetus to adult levels at 2-3 weeks of age; this increase correlates with the maximal expression of V1 during the same period. Expression of the V1 isomyosin can be eliminated in the neonatal rat if endogenous thyroid hormone synthesis is suppressed by propylthiouracil (PTU) treatment. In the PTU-treated rats, V3 is the only isomyosin synthesized between 1 and 30 days of age. In fetal ventricle, the amount of V1 is also decreased but not completely eliminated by PTU treatment. Conversely, the relative amount of V1 can be increased in the fetal ventricle by increasing the fetal serum concentrations of T4 and T3 to adult physiological levels. In these fetal ventricles, V1 represents greater than 85% of the total myosin. Likewise, the expression and accumulation of V1 could be stimulated in ventricles of PTU-treated, 12-day-old rats by administration of pharmacological or physiological doses of T3. Within 4 to 8 h after an initial dose of T3, V1 accumulates to 5-10% of the ventricular myosin, and by 72 h comprises 60-80% of the myosin. These results indicate that endogenous thyroid hormone induces the synthesis of ventricular heavy chain alpha, which as a dimer forms the V1 isomyosin, or plays a permissive role for the continued synthesis of heavy chain alpha in ventricles of fetal and neonatal rats.