Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis
Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis
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DOI：
10.1210/en.2007-0652
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发表时间：
2007-12-01
期刊：
影响因子：
4.8
通讯作者：
Germain, Donald L. St.
中科院分区：
文献类型：
--
作者：
Hernandez, Arturo;Martinez, M. Elena;Germain, Donald L. St.
3型脱碘酶（D3）是一种失活甲状腺激素的硒酶，在发育期间和成人中枢神经系统中高度表达。我们最近观察到缺乏D3活性的小鼠（D3 KO小鼠）在成年后发生围产期甲状腺毒症，随后出现提示中枢性甲状腺功能减退的激素水平模式。在这份报告中，我们描述了额外的研究结果，旨在调查在这个独特的动物模型中的甲状腺轴的调节。我们的研究结果表明，D3 KO小鼠的甲状腺和垂体腺不适当地响应TSH和TRH刺激，分别。此外，在通过抗甲状腺治疗诱导严重甲状腺功能减退症后，D3 KO小鼠中血清TSH的升高仅为野生型小鼠中观察到的升高的15%。此外，D3 KO动物严重甲状腺功能减退不能显示预期的下丘脑室旁核中前TRH原mRNA的增加。最后，用T-3处理导致D3 KO小鼠中的血清T-3水平比野生型小鼠中的高得多.这伴随着突变动物的显著体重减轻和致死性。总之，缺乏D3活性导致T-3清除受损，并在所有水平（下丘脑、垂体和甲状腺）调节甲状腺轴的机制中存在显著缺陷。
The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild- type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro- TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T-3 results in a serum T-3 level in D3KO mice that is much higher than that in wild- type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T-3 and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.