Araujo R L, Andrade B M, da Silva M L, Ferreira A C F, Carvalho D P
Instituto de Biofísica Carlos Chagas Filho, CCS-Bloco G-Cidade Universitária, Rio de Janeiro, 21949-900, Brazil.
Am J Physiol Endocrinol Metab. 2009 May;296(5):E1157-63. doi: 10.1152/ajpendo.90869.2008. Epub 2009 Feb 10.
The relationship between thyroid function and leptin has been extensively studied; however, the mechanisms underlying the changes in thyroid hormone economy that occur during caloric deprivation remain elusive. Our goal was to evaluate the thyroid function of rats submitted to 40% food restriction after chronic leptin replacement. Caloric restriction for 25 days led to significantly reduced serum leptin, thyroid-stimulating hormone (TSH), thyroxine (T(4)), and triiodothyronine (T(3)) and increased serum corticosterone, while liver, kidney, and thyroid type I deiodinase (D1) and brown adipose tissue (BAT) type II deiodinase (D2) activities were decreased and hypothalamic D2 was significantly increased. Interestingly, thyroid iodide uptake was unchanged by caloric restriction, but thyroperoxidase (TPO) activity was significantly reduced. Leptin replacement for the last 10 days of caloric restriction normalized serum leptin and TSH levels, but serum T(4) and T(3) levels and thyroid D1 and TPO activities were not reestablished. Also, a negative effect of leptin administration on Na(+)-I(-) symporter function was detected. Liver and kidney D1 and hypothalamic and BAT D2 were normalized by leptin, while pituitary D2 was significantly decreased. In conclusion, a tissue-specific modulation of deiodinases might be implicated in the normalization of thyroid function during leptin replacement in food-restricted rats. Although leptin restores the hypothalamus-pituitary axis during food restriction, it exerts a direct negative effect on the thyroid gland; thus normalization of serum thyroid hormones might depend on changes in deiodinase activities and the long-term thyroid stimulation by TSH to counterbalance the direct negative effects of leptin on the thyroid gland.
甲状腺功能与瘦素之间的关系已得到广泛研究；然而，热量限制期间甲状腺激素代谢变化的潜在机制仍不清楚。我们的目标是评估慢性瘦素替代后接受40%食物限制的大鼠的甲状腺功能。25天的热量限制导致血清瘦素、促甲状腺激素（TSH）、甲状腺素（T4）和三碘甲状腺原氨酸（T3）显著降低，血清皮质酮升高，而肝脏、肾脏和甲状腺Ⅰ型脱碘酶（D1）以及棕色脂肪组织（BAT）Ⅱ型脱碘酶（D2）活性降低，下丘脑D2显著升高。有趣的是，热量限制未改变甲状腺碘摄取，但甲状腺过氧化物酶（TPO）活性显著降低。在热量限制的最后10天进行瘦素替代可使血清瘦素和TSH水平恢复正常，但血清T4和T3水平以及甲状腺D1和TPO活性未恢复。此外，检测到瘦素给药对钠-碘同向转运体功能有负面影响。瘦素使肝脏和肾脏D1以及下丘脑和BAT D2恢复正常，而垂体D2显著降低。总之，脱碘酶的组织特异性调节可能与食物限制大鼠瘦素替代期间甲状腺功能的正常化有关。尽管瘦素在食物限制期间可恢复下丘脑-垂体轴，但它对甲状腺产生直接负面影响；因此，血清甲状腺激素的正常化可能取决于脱碘酶活性的变化以及TSH对甲状腺的长期刺激，以抵消瘦素对甲状腺的直接负面影响。
