Rastogi R B, Singhal R L
J Pharmacol Exp Ther. 1976 Sep;198(3):609-18.
In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.
在新生大鼠中，连续30天给予左旋三碘甲状腺原氨酸（10微克/100克/天）会出现甲状腺功能亢进的迹象，包括伴随成熟过程各种身体和行为特征的加速发育。自发运动活动增加了69%。发育中的大鼠暴露于甲状腺激素下，显著增加了纹状体酪氨酸的内源性浓度、酪氨酸羟化酶的活性以及几个脑区中多巴胺的水平。多巴胺的主要代谢产物纹状体高香草酸和3,4 - 二羟基苯乙酸的浓度也增加了，且变化幅度大于多巴胺的升高幅度。尽管酪氨酸羟化酶的活性增加以及底物酪氨酸的可用性提高，但除小脑外，大脑各区域去甲肾上腺素的稳态水平保持不变。此外，新生期甲状腺功能亢进显著增加了中脑色氨酸水平和色氨酸羟化酶活性，但除下丘脑和小脑色氨酸浓度略有降低外，几个离散脑区的5 - 羟色胺水平没有变化。然而，下丘脑、脑桥延髓、中脑、纹状体和海马体中5 - 羟吲哚乙酸水平升高。5 - 羟吲哚乙酸水平升高似乎并非由于5 - 羟色胺神经元内脱氨基作用增强，因为甲状腺功能亢进大鼠的大脑皮质和中脑单胺氧化酶活性未受影响。数据表明，甲状腺功能亢进显著增加了成熟大脑中儿茶酚胺和5 - 羟色胺的合成及利用。由于已知成熟大脑对甲状腺激素作用的反应与发育中大脑不同，因此也研究了左旋三碘甲状腺原氨酸处理对成年大鼠各种假定神经体液的影响。给120日龄大鼠连续30天给予左旋三碘甲状腺原氨酸（10微克/100克/天），酪氨酸水平增加了23%，色氨酸水平增加了43%，但色氨酸羟化酶活性未观察到明显变化。与新生期甲状腺功能亢进不同，成年大鼠甲状腺激素过量未使运动活动产生任何变化，仅使纹状体酪氨酸羟化酶活性略有下降。除中脑多巴胺浓度上升19%外，大脑所有区域多巴胺浓度均保持不变。下丘脑、脑桥延髓和中脑去甲肾上腺素浓度发生改变，而纹状体和小脑5 - 羟色胺及其代谢产物5 - 羟吲哚乙酸水平显著降低。由于多巴胺能和去甲肾上腺素能神经元是运动系统的关键组成部分，因此在幼年左旋三碘甲状腺原氨酸处理的动物中，行为活动增加可能与神经元组织中儿茶酚胺周转增加有关。
