摘要
甲状腺功能与碘摄入水平有密切的关系,甲状腺功能主要是通过其合成的甲状腺激素来实现的.脱碘反应是调节甲状腺激素生物活性的重要方式,不同碘营养状态下甲状腺组织Ⅰ型脱碘酶(D1)基因表达及活性的变化是甲状腺功能调节的重要机制.在成功建立碘缺乏与不同程度碘过量的Babl/c小鼠模型的基础上,采用实时荧光定量PCR法检测甲状腺组织D1mRNA表达水平,同时以125I-rT3作为底物,结合离子交换层析技术测定甲状腺D1活性,此外,应用竞争结合放射免疫分析方法对甲状腺组织激素进行了检测.结果显示:碘缺乏时,D1mRNA表达和D1活性均显著升高,甲状腺组织内T3与T4水平均显著降低,但T3/T4明显升高;碘过量可明显抑制D1mRNA表达,但对D1活性并无显著影响,甲状腺组织内T3/T4有所下降.上述结果提示,甲状腺Ⅰ型脱碘酶在甲状腺功能调节中具有重要的作用,碘缺乏时D1mRNA表达及活性的上调可促进T4向T3的转化,以满足机体代谢的需要,而过量碘对D1基因表达的抑制可防止过多的T3对机体的损伤,具有重要的生理意义.
Thyroid function ultimately depends on appropriate iodine supply to the gland. Thyroid hormone deiodination is an intrinsic component of the thyroid hormone homeostasis. Type I iodothyronine deiodinase （D1） plays an important role in thyroid hormone metabolism and has close relationship with thyroid function. Based on successfully establishing animal models of iodine deficiency and iodine excess in Babl/c mice （Babl/c mice were randomly divided into five groups： low iodine （LI）, normal iodine （NI）, five-fold iodine （SHI）, ten-fold iodine （10HI） and fifty-fold iodine （50HI） group. Three months and six months after admistration, they were sacrificed and thyroids were excised）, the expression level of D l mRNA were examined by using real time quantitative PCR method. DI activity was analyzed by ^125I-rT3 as substrate combined with ion-exchange chromatography. The thyroid hormone was measured with radioimmunoassay method. The data revealed that in the case of iodine deficiency, both D1 mRNA expression and D1 activity was greatly increased（compared with NI groups, P 〈 0.01）. T3 and T4 in thyroid tissue was significantly decreased, but T3 / T4 was increased （P 〈 0.01）. On the other hand, when faced to iodine excess, D l mRNA expression was reduced （There was a tendency of decreasing in D l mRNA expression in all HI groups compared with NI group, significant difference was found in 5HI and 50HI at 6 months ）, while there was no remarkable effect on D1 activity. The thyroid hormone assay showed that T3 / T4 was decreased. In conclusion, D l is a critical factor in the regulation mechanism of thyroid function. The up-regulated mRNA expression and activity under the state of iodine deficiency will improve the conversion ofT4 to T3 to maintain the normal thyroid function. The inhibition olD1 expression induced by iodine excess may be taken as an effective way to protect organism from impairment caused by too much T3.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2008年第3期320-326,共7页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金重点资助项目(30230330)
天津市科技发展计划项目(05YFGDSF02700)~~
关键词
Ⅰ型脱碘酶
甲状腺激素
基因表达
甲状腺功能
type I iodothyronine deiodinase, thyroid hormone, gene expression, thyroid function
