Fasting-induced increase in type II iodothyronine deiodinase activity and messenger ribonucleic acid levels is not reversed by thyroxine in the rat hypothalamus
Fasting-induced increase in type II iodothyronine deiodinase activity and messenger ribonucleic acid levels is not reversed by thyroxine in the rat hypothalamus
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DOI：
10.1210/en.139.6.2879
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发表时间：
1998-06-01
期刊：
影响因子：
4.8
通讯作者：
Horvath, TL
中科院分区：
文献类型：
--
作者：
Diano, S;Naftolin, F;Horvath, TL
T-3 局部形成在甲状腺对下丘脑 TRH 产生细胞的反馈作用中的重要性已经确定。甲状腺原发性衰竭会导致循环 T-4 和 T-3 水平下降，导致下丘脑室旁核中 TRH 的产生和释放升高。相反，在短期禁食期间，甲状腺激素血浆水平下降与 TRK 产生和释放受到抑制同时发生。在大脑中，将 T-4 转化为 T-3 的普遍酶是 II 型碘甲状腺氨酸脱碘酶 (DII)。本研究旨在确定禁食大鼠和由于甲状腺功能衰竭而导致甲状腺功能减退的动物中是否可能存在 II 型脱碘酶下丘脑的差异表达。使用原位杂交，我们评估了大鼠下丘脑中 II 型脱碘酶信使 RNA (mRNA) 的水平，这些大鼠是甲状腺正常、甲状腺功能亢进 (T-4)、丙硫氧嘧啶 (PTU) 诱导的甲状腺功能减退并禁食的大鼠。一组禁食的大鼠还接受了外源性 T-4。 DII mRNA 在第三脑室周围检测到，包括室管膜层和邻近的脑室周围区域以及弓状核和正中隆起的外层。定量原位杂交分析表明，与甲状腺功能正常的对照组相比，PTU 治疗和短期禁食导致 DII 信使水平显着升高。服用 PTU 三周后，循环 T-3 水平持续下降，T-4 水平检测不到，而禁食 3 天，血清甲状腺激素浓度仅下降 50%。然而有趣的是，与 PTU 处理的大鼠相比，禁食动物中 DII mRNA 的表达量高出一倍多。此外，虽然在甲状腺功能正常的动物中，T-4给药抑制了DII mRNA表达，但相同的治疗对禁食诱导的DII信息升高没有影响。 为了评估DII酶活性在食物剥夺期间是否也受到影响，解剖下丘脑，并在甲状腺功能正常的对照大鼠、禁食大鼠和禁食加T-4治疗的大鼠中测量DII活性。为了确定禁食和 PTU 治疗引起的血浆甲状腺激素水平的可比较变化是否会以类似的方式影响 DII 酶活性，给动物腹腔注射 PTU 5 天，以将血浆甲状腺激素降低到与禁食引起的水平相似的水平。 DII 酶测定显示，与甲状腺功能正常的对照组和 PTU 治疗的大鼠相比，禁食和禁食加 T-4 治疗的动物的 DII 活性显着增加。与甲状腺功能正常的动物相比，PTU 治疗的大鼠没有发现显着变化。这些数据表明，在短期禁食期间，非甲状腺来源的信号是下丘脑 DII 产生和活性大幅升高的基础。因此，我们提出，在食物匮乏的初始阶段，由于局部形成的 T-3，下丘脑上存在甲状腺负反馈增加。在这些条件下，这种局部甲状腺功能亢进反过来可能会导致 TRH 受到抑制。
The importance of local formation of T-3 in the feedback effect of the thyroid gland on hypothalamic TRH-producing cells has been established. Primary failure of the thyroid gland results in a fall in circulating T-4 and T-3 levels, leading to an elevation in the production and release of TRH in the hypothalamic paraventricular nucleus. In contrast, during short term fasting, declining plasma levels of thyroid hormones coincide with suppressed TRK production and release. In the brain, the prevalent enzyme that converts T-4 to T-3 is type II iodothyronine deiodinase (DII). The present study was undertaken to determine whether a differential hypothalamic expression of type II deiodinase may exist in fasted rats and in animals that are hypothyroid due to the failure of the thyroid gland. Using in situ hybridization, we assessed type II deiodinase messenger RNA (mRNA) levels in the hypothalamus of rats that were control euthyroid, hyperthyroid (T-4), hypothyroid induced by propylthiouracil (PTU), and fasted. A group of fasted rats also received exogenous T-4. DII mRNA was detected around the third ventricle, including the ependymal layer and adjacent periventricular regions as well as in the arcuate nucleus and the external layer of the median eminence. Quantitative in situ hybridization analysis demonstrated that PTU treatment and short term fasting resulted in significant elevations in DII messenger levels compared with those in euthyroid controls. Three weeks of PTU administration induced a consistent decline in circulating T-3 and undetectable T-4 levels, whereas 3 days of fasting resulted in only a 50% fall in the concentration of serum thyroid hormones. Interestingly, however, the expression of the DII mRNA was more than a-fold higher in fasted animals compared with the values in PTU-treated rats. Furthermore, although T-4 administration repressed DII mRNA expression in euthyroid animals, the same treatment had no effect on the fasting-induced elevations of DII message.To assess whether DII enzymatic activity is also affected during food deprivation, hypothalami were dissected out, and DII activity was measured in control euthyroid, fasted, and fasted plus T-4-treated rats. To determine whether comparable changes in plasma thyroid hormone levels induced by fasting and PTU treatment could have affected DII enzymatic activity in a similar manner, animals were injected ip with PTU for 5 days to decrease plasma thyroid hormones to levels similar to those caused by fasting. DII enzymatic assay showed a significant increase in DII activity in fasted and fasted plus T-4-treated animals compared with those in euthyroid controls and PTU-treated rats. No significant changes were found in PTU-treated rats compared with euthyroid animals. These data indicate that during short term fasting, a signal of nonthyroid origin underlies the robust elevation of DII production and activity in the hypothalamus. Thus, we propose that during the initial phase of food deprivation, an increased negative thyroid feedback exists on the hypothalamus due to locally formed T-3. This local hyperthyroidism may, in turn, induce the suppression of TRH under these conditions.