Rondeel J M, de Greef W J, Klootwijk W, Visser T J
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Endocrinology. 1992 Feb;130(2):651-6. doi: 10.1210/endo.130.2.1733713.
The aim of this study was to investigate whether the severity and duration of primary hypothyroidism influence hypothalamic TRH release. Hypothyroidism was induced in male Wistar rats by treatment with different thyrostatic drugs or by thyroidectomy. Serum TSH in rats treated for up to 3 weeks with methimazole (MMI; 0.05% in drinking water) increased 20-fold, but TRH release into hypophyseal portal blood (HPB) did not change. Treatment with propylthiouracil (PTU; 0.1% in drinking water), which inhibits thyroidal T4 production and peripheral conversion of T4 to T3, resulted in a more rapid reduction in serum T3 levels and increase in serum TSH than those in rats treated with 0.1% MMI. Although these differences were no longer observed after 3 weeks of treatment, TRH release into HPB of rats treated with PTU was 34-49% higher than that in MMI-treated rats. Combined treatment with MMI (0.05-0.1% in drinking water) and iopanoic acid (IOP; 4 mg/100 g BW.day, ip), an inhibitor of both peripheral and central T4 to T3 conversion, also tended to produce a more rapid decrease in serum T3 and increase in serum TSH. After 3 weeks of treatment, serum T4, T3, and TSH were not different in the two groups, but TRH release into HPB was 48-65% increased by MMI plus IOP vs. MMI alone. Three to 10 weeks after thyroidectomy, TRH release into HPB was 58-72% higher than that in untreated controls. In vitro incubation of hypothalami isolated from rats treated for 3 weeks with MMI, MMI plus IOP, or PTU, as described above, showed that basal and 56 mM K(+)-induced TRH release were not influenced by the different drugs. Also, the total hypothalamic TRH content was not changed by any of these treatments. However, in rats treated for 1 or 2 weeks with MMI or PTU, the TRH content of the median eminence was decreased by 17-25%. These findings indicate that, depending on severity and duration, experimental hypothyroidism may cause a significant increase in hypothalamic TRH release in rats. The magnitude of these changes compared with the much larger increases in serum TSH suggests that the feedback of thyroid hormone on TSH secretion is mainly exerted at the pituitary level.
本研究的目的是调查原发性甲状腺功能减退症的严重程度和持续时间是否会影响下丘脑促甲状腺激素释放激素（TRH）的释放。通过用不同的抗甲状腺药物治疗或进行甲状腺切除术，在雄性Wistar大鼠中诱发甲状腺功能减退症。用甲巯咪唑（MMI；饮用水中含0.05%）治疗长达3周的大鼠，其血清促甲状腺激素（TSH）升高了20倍，但进入垂体门脉血（HPB）的TRH释放没有变化。用丙硫氧嘧啶（PTU；饮用水中含0.1%）治疗，该药物抑制甲状腺T4的产生以及T4向T3的外周转化，与用0.1%MMI治疗的大鼠相比，导致血清T3水平下降更快，血清TSH升高。尽管在治疗3周后不再观察到这些差异，但用PTU治疗的大鼠HPB中TRH的释放比用MMI治疗的大鼠高34 - 49%。联合使用MMI（饮用水中含0.05 - 0.1%）和碘番酸（IOP；4mg/100g体重·天，腹腔注射），一种外周和中枢T4向T3转化的抑制剂，也倾向于使血清T3更快下降和血清TSH升高。治疗3周后，两组的血清T4、T3和TSH没有差异，但与单独使用MMI相比，MMI加IOP使HPB中TRH的释放增加了48 - 65%。甲状腺切除术后3至10周，HPB中TRH的释放比未治疗的对照组高58 - 72%。如上述，对用MMI单独、MMI加IOP或PTU治疗3周的大鼠分离出的下丘脑进行体外培养，结果显示基础状态和56mM钾诱导的TRH释放不受不同药物的影响。此外，这些处理中的任何一种都未改变下丘脑TRH的总含量。然而，在用MMI或PTU治疗1或2周的大鼠中，正中隆起的TRH含量下降了17 - 25%。这些发现表明，根据严重程度和持续时间，实验性甲状腺功能减退症可能导致大鼠下丘脑TRH释放显著增加。与血清TSH的大幅升高相比，这些变化的幅度表明甲状腺激素对TSH分泌的反馈主要在垂体水平发挥作用。
