Role of thyroid hormones in early postnatal development of skeletal muscle and its implications for undernutrition.
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), soleus and rhomboideus. Reductions in plasma concentrations of thyroxine (T4; 32%, P < 0.01), triiodothyronine (T3; 48%, P < 0.001), free T3 (58%, P < 0.001) and hepatic 5'-monodeiodinase (EC 1.11.1.8) 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, in l. dorsi (2%, P < 0.01) and soleus (7%, P < 0.01). Nuclear T3-receptor concentration in l. dorsi of 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 (EC 3.6.1.37) concentration was reduced by 15-16% in all muscles (l. dorsi P < 0.05, soleus P < 0.001, rhomboideus P < 0.05), and Ca(2+)-ATPase (EC 3.6.1.38) concentration was significantly reduced in the two slow-twitch muscles: by 22% in rhomboideus (P < 0.001) and 23% in soleus (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.
Harrison
A P
AP
Department of Cellular Physiology, Babraham Institute, Cambridge, Denmark.
Tivey
D R
DR
Clausen
T
T
Duchamp
C
C
Dauncey
M J
MJ
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D007480:Iopanoic Acid / Q000494:pharmacology; D008713:Methimazole / Q000494:pharmacology; D008954:Models, Biological; D024510:Muscle Development; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D009748:Nutrition Disorders / Q000503:physiopathology*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine / Q000254:growth & development* / Q000378:metabolism; D013963:Thyroid Hormones / Q000502:physiology*; D014284:Triiodothyronine / Q000378:metabolism
D013956:Antithyroid Agents; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D008713:Methimazole; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D007480:Iopanoic Acid