Dupont A, Dussault J H, Rouleau D, DiPaolo T, Coulombe P, Gagné B, Mérand Y, Moore S, Barden N
Endocrinology. 1981 Jun;108(6):2039-45. doi: 10.1210/endo-108-6-2039.
The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the development of catecholamine-, TRH-, and substance P-containing neurons in discrete rat brain nuclei were studied. Newborn male rats were rendered hypothyroid by the injection of 125 muCi 131I and, after 45 days, were compared with normal littermate controls and 131I-injected animals subsequently maintained on T4 injections. The peptide or catecholamine content of discrete brain nuclei removed by punches of frozen brain slices was measured by RIA or radioenzymatic assay, respectively. The success of the thyroidectomy was verified by criteria of weight, length, plasma T4, and pituitary GH content. Animals receiving T4 replacement therapy were indistinguishable from normal littermates. Substance P was measured in 32 different brain nuclei and was significantly increased in 19 of these areas in hypothyroid animals. No changes in norepinephrine were detected, and the dopamine content of all but 3 brain nuclei was increased by thyroidectomy. The TRH concentration was drastically reduced in the median eminence of hypothyroid animals and also changed in 3 other extrahypothalamic areas. All of the changes seen in catecholamine, TRH, and substance P distribution in hypothyroid animals were completely reversed by T4 replacement therapy. These results demonstrate changes in brain peptide neurotransmitters during the hypothyroid state and open new vistas for comprehension of biochemical mechanisms underlying central nervous system malfunction.
研究了新生大鼠甲状腺切除及甲状腺激素替代疗法对大鼠离散脑核中含儿茶酚胺、促甲状腺激素释放激素（TRH）和P物质的神经元发育的影响。给新生雄性大鼠注射125μCi的131I使其甲状腺功能减退，45天后，将其与正常同窝对照大鼠以及随后接受T4注射的131I注射大鼠进行比较。分别通过放射免疫分析（RIA）或放射酶法测定冷冻脑片打孔取出的离散脑核中的肽或儿茶酚胺含量。通过体重、体长、血浆T4和垂体生长激素含量标准来验证甲状腺切除是否成功。接受T4替代疗法的动物与正常同窝动物无明显差异。在32个不同脑核中测量了P物质，甲状腺功能减退动物的这些区域中有19个区域的P物质显著增加。未检测到去甲肾上腺素的变化，除3个脑核外，甲状腺切除使所有脑核中的多巴胺含量增加。甲状腺功能减退动物正中隆起处的TRH浓度大幅降低，其他3个下丘脑外区域也发生了变化。甲状腺功能减退动物中儿茶酚胺、TRH和P物质分布的所有变化都通过T4替代疗法完全逆转。这些结果证明了甲状腺功能减退状态下脑肽神经递质的变化，并为理解中枢神经系统功能障碍的生化机制开辟了新的前景。
