Harrison A P, Tivey D R, Clausen T, Duchamp C, Dauncey M J
Department of Cellular Physiology, Babraham Institute, Cambridge, Denmark.
Br J Nutr. 1996 Dec;76(6):841-55. doi: 10.1079/bjn19960091.
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.
能量摄入对许多内分泌轴有深远影响，而这些内分泌轴又在发育过程中发挥核心作用。在大型哺乳动物出生后的早期生活中，已评估了一段类似于营养不良所致的短期轻度甲状腺功能减退对调节肌肉发育的具体影响。通过在4至14日龄仔猪的饲料中添加甲巯咪唑和碘番酸来诱发甲状腺功能减退，对照组则按其甲状腺功能减退同窝仔猪的能量摄入量进行配对饲养。评估甲状腺状态，然后在以下功能不同的肌肉中评估肌纤维分化和阳离子泵浓度：背最长肌、比目鱼肌和菱形肌。治疗后，血浆甲状腺素（T4；降低32%，P<0.01）、三碘甲状腺原氨酸（T3；降低48%，P<0.001）、游离T3（降低58%，P<0.001）和肝脏5'-单脱碘酶（EC 1.11.1.8）活性（降低74%，P<0.001）均出现下降。轻度甲状腺功能减退时，背最长肌（2%，P<0.01）和比目鱼肌（7%，P<0.01）中I型慢肌氧化纤维的比例虽有小幅但显著的增加。与对照组相比，甲状腺功能减退动物背最长肌中的核T3受体浓度增加了46%（P<0.001），这种反应可能代表一种稳态机制，使肌肉对低水平的循环甲状腺激素更敏感。然而，所有肌肉中的Na+，K(+)-ATP酶（EC 3.6.1.37）浓度均降低了15 - 16%（背最长肌P<0.05，比目鱼肌P<0.001，菱形肌P<0.05），并且在两块慢肌中Ca(2+)-ATP酶（EC 3.6.1.38）浓度显著降低：菱形肌降低22%（P<0.001），比目鱼肌降低23%（P<0.05）。得出的结论是，在大型哺乳动物出生后的早期发育过程中，一段与营养不良时相当的轻度甲状腺功能减退时期会诱导肌纤维分化发生变化，并导致骨骼肌中阳离子泵的下调。这些变化会导致运动迟缓、肌肉无力，还会减少ATP水解，同时提高能量效率。
