A Protective Role for Type 3 Deiodinase, a Thyroid Hormone-Inactivating Enzyme, in Cochlear Development and Auditory Function
A Protective Role for Type 3 Deiodinase, a Thyroid Hormone-Inactivating Enzyme, in Cochlear Development and Auditory Function
复制标题
DOI：
10.1210/en.2008-1419
复制
发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Forrest, Douglas
中科院分区：
文献类型：
--
作者：
Ng, Lily;Hernandez, Arturo;Forrest, Douglas
甲状腺激素是耳蜗发育和听觉功能所必需的，但控制这些过程的因素知之甚少。先前的证据表明，在小鼠中，甲状腺激素的血清供应通过2型脱碘酶本身在耳蜗内增加，2型脱碘酶在听力开始之前放大甲状腺激素的活性形式T-3的水平。我们现在报告说，3型脱碘酶，甲状腺癌失活酶编码的Dio 3，表达在未成熟的耳蜗前2型脱碘酶。Dio 3（-/-）小鼠表现出听觉缺陷和耳蜗分化加速，与2型脱碘酶缺失引起的发育迟缓形成对比。Dio 3 mRNA在大上皮嵴、血管纹和螺旋神经节中的表达模式与甲状腺激素受体β（TR β）的表达模式部分重叠，TR β是主要负责听觉发育的T3受体。3型脱碘酶防止TR β过早刺激的提议通过删除TR β得到支持，这将Dio 3（-/-）耳蜗表型从加速分化之一转化为延迟分化之一。结果表明3型脱碘酶在听力中具有保护作用。听觉系统说明了组织可以通过2型和3型脱碘酶自动调节其对甲状腺激素的发育反应的程度。（内分泌学150：1952-1960，2009）
Thyroid hormone is necessary for cochlear development and auditory function, but the factors that control these processes are poorly understood. Previous evidence indicated that in mice, the serum supply of thyroid hormone is augmented within the cochlea itself by type 2 deiodinase, which amplifies the level of T-3, the active form of thyroid hormone, before the onset of hearing. We now report that type 3 deiodinase, a thyroid hormone-inactivating enzyme encoded by Dio3, is expressed in the immature cochlea before type 2 deiodinase. Dio3(-/-) mice display auditory deficits and accelerated cochlear differentiation, contrasting with the retardation caused by deletion of type 2 deiodinase. The Dio3 mRNA expression pattern in the greater epithelial ridge, stria vascularis, and spiral ganglion partly overlaps with that of thyroid hormone receptor beta (TR beta), the T3 receptor that is primarily responsible for auditory development. The proposal that type 3 deiodinase prevents premature stimulation of TR beta was supported by deleting TR beta, which converted the Dio3(-/-) cochlear phenotype from one of accelerated to one of delayed differentiation. The results indicate a protective role for type 3 deiodinase in hearing. The auditory system illustrates the considerable extent to which tissues can autoregulate their developmental response to thyroid hormone through both type 2 and 3 deiodinases. (Endocrinology 150: 1952-1960, 2009)