Early responses of skeletal muscle in recovery from hypothyroidism

Postnatal growth of skeletal muscle (m. gastrocnemius) was compared in rats under euthyroid, hypothyroid and hypothyroid-rehabilitated conditions. In normal (euthyroid) animals, gastrocnemius muscle grows significantly in terms of weight (150 x) from birth to the young adult and, in terms of total contractile myofibril protein (15 x) and myosin ATPase activity (10 x) between days 25 and 90. Rats made hypothyroid (with 0.1% w/v propylthiouracil, PTU) from birth show reduced growth. At 25 days (weaning), compared with euthyroid, muscle weight is only 25% of normal, and a similar reduction is found in total DNA, RNA, protein, myofibril protein, and myosin ATPase activity. These deficits, already significant by day 10, are more marked by day 50 due to the near arrest of growth. Hypothyroid rats allowed to recover by PTU withdrawal after day 25 (rehabilitated) undergo marked compensatory muscle growth. By day 90, muscle weight and protein content increase 50 x, DNA 7 x and RNA 17 x. Over this period, total myofibrillar protein and myosin ATPase increase 20-40 x, but are still below those of 90-day controls, suggesting that the severe growth retardation had not yet been fully compensated. Early thyroid deficiency drastically reduces the normal age-related growth of skeletal muscle and severely retards the development of contractile elements, affecting muscle hypertrophy (protein content) more than cell proliferation (DNA content). Rehabilitation compensates to a major degree for this growth retardation. These results underline the key role of thyroid hormones in regulating development and maturation of skeletal muscle throughout the preweaning and postweaning phases of growth.