Role of thyroid hormones in early postnatal development of skeletal muscle and its implications for undernutrition

Abstract

Energy intake profoundly influences many endocrine axes which in turn play a central role in development. The specific influence of a short period of mild hypothyroidism, similar to that induced by undernutrition, in regulating muscle development has been assessed in a large mammal during early postnatal life. Hypothyroidism was induced by providing methimazole and iopanoic acid in the feed of piglets between 4 and 14 d of age, and controls were pair-fed to the energy intake of their hypothyroid littermates. Thyroid status was evaluated, and myofibre differentiation and cation pump concentrations were then assessed in the following functionally distinct muscles:longissimus dorsi(l. dorsi),soleusandrhomboideus. Reductions in plasma concentrations of thyroxine (T4; 32%,P< O·Ol), triiodothyronine (T3;48%,P< 0·001), free T3, (58%,P< 0·001)and hepatic 5'-monodeiodinase (EC1.11.1.8) activity (74%,P< 0·001) occurred with treatment. Small, although significant, increases in the proportion of type I slow-twitch oxidative fibres occurred with mild hypothyroidism, inl. dorsi(2%,P< 0·01) andsoleus(7%,P< 0·01). Nuclear T3-receptor concentration inl. dorsiof hypothyroid animals compared with controls increased by 46% (P< 0·001), a response that may represent a homeostatic mechanism making muscle more sensitive to low levels of circulating thyroid hormones. Nevertheless, Na+, K+-ATPase (EC3.6.1.37) concentration was reduced by 15–16% in all muscles (l.dorsiP< 0·05,soleusP< 0·001,rhomboideusP< 0·05), and Ca2+-ATPase (EC3.6.1.38) concentration was significantly reduced in the two slow-twitch muscles: by 22% inrhomboideus(P< 0·001) and 23% insoleus(P< 0·05). It is concluded that during early postnatal development of large mammals a period of mild hypothyroidism, comparable with that found during undernutrition, induces changes in myofibre differentiation and a down-regulation of cation pumps in skeletal muscle. Such changes would result in slowness of movement and muscle weakness, and also reduce ATP hydrolysis with a concomitant improvement in energetic efficiency.