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TSH는 NIS의 발현을 유도하며, 요오드는 NIS의 기능을 저하시켰다. 요오드에 의한 NIS의 분자생물학적인 조절 기전에는 NIS의 전사 및 전이과정 의 조절과 더불어 전이후 과정이 매우 중요한 역할을 담 당하고 있는 것으로 생각된다. 요 약 목적 : Sodium-iodide symporter (NIS)는 갑상선호 르몬의 생합성에 이용되는 요오드를 갑상선 내로 섭취시 키는 역할을 담당하고 있는 중요한 당단백질로서 세포막 에 위치해있다. 그러나 요오드가 NIS의 기능을 조절하는 기전에 대해서는 잘 밝혀져 있지 않은데, 최근에는 전사 후 과정 중의 변화가 중요한 조절 기전일 가능성이 제시 되기도 하였다. 그러므로 본 연구에서는 FRTL-5 갑상선 세포에 요오드가 요오드 섭취능, NIS mRNA, 단백의 발 현 등에 미치는 영향을 분석하여, 요오드가 NIS의 활성 도를 조절하는 기전을 규명하고자 하였다. 방법 및 결과 : TSH는 농도와 시간에 비례하여 NIS 의 요오드 섭취능과 NIS mRNA 발현을 증가시켰다. 백 서에서 메치마졸 투여로 TSH를 상승시킨 후 면역화학 염색으로 관찰한 NIS 단백도 세포에서와 마찬가지로 증 가되어 있었다. 한편, 요오드를 처리하였을 때에 1 mM NaI까지 농도에 비례하여 FRTL-5 세포의 요오드 섭취 능이 감소하였으나, NIS mRNA의 발현에는 거의 변화 가 없었다. 다만, 10 mM 이상의 농도에서는 24시간째에 일시적으로 NIS mRNA의 발현의 감소가 관찰되었다. 한편, 면역화학염색을 통하여 살펴본 NIS 단백의 양은 NaI를 처리하였을 때에 처음 24시간까지는 감소하였으 나 이후 다시 증가하여 48시간째에는 기저 수준의 50% 이상 회복되었다.


Background : The sodium-iodide symporter (NIS) is a key plasma membrane glycoprotein that mediates active iodide transport in the thyroid gland. Whereas relatively little is known about the mechanisms by which iodide regulates NIS activity, post-transcriptional events have been suggested to play a role. Methods : We have attempted to determine the mechanism responsible for the regulation of NIS by determining NIS mRNA and NIS protein levels accompany with measuring NIS activities in FRTL-5 thyroid cells or Sprague-Dawley rats. Results : TSH increased the iodide uptake capacities and the expression of NIS mRNA by timeand concentration-dependent manner. This finding was also true in Sprague-Dawley rats whose serum TSH were elevated by prolonged methimazole administration; the expression of NIS protein was increased in TSH-elevated rats. On the other hands, iodide suppressed the NIS activity by concentration-dependent manner till 1 mM of NaI. But, the amounts of NIS mRNA were not changed, although those were transiently decreased at 24 hours after iodide treatment at the higher concentration of NaI, 10 mM or over. The amounts of NIS protein, which were analyzed by immunohistochemstry, were decreased till first 24 hours, but those were re-increased, the amounts at 48 hours after iodide treatment returned to more than 50% of basal levels. Conclusion : TSH induced the expression of NIS, while iodide inhibited the NIS activities. Our finding suggested that the excessive iodide regulates the NIS activity, at least in part, through post-translational as well as transcriptional and translational mechanisms.(Korean J Med 65:549-557, 2003)


Background : The sodium-iodide symporter (NIS) is a key plasma membrane glycoprotein that mediates active iodide transport in the thyroid gland. Whereas relatively little is known about the mechanisms by which iodide regulates NIS activity, post-transcriptional events have been suggested to play a role. Methods : We have attempted to determine the mechanism responsible for the regulation of NIS by determining NIS mRNA and NIS protein levels accompany with measuring NIS activities in FRTL-5 thyroid cells or Sprague-Dawley rats. Results : TSH increased the iodide uptake capacities and the expression of NIS mRNA by timeand concentration-dependent manner. This finding was also true in Sprague-Dawley rats whose serum TSH were elevated by prolonged methimazole administration; the expression of NIS protein was increased in TSH-elevated rats. On the other hands, iodide suppressed the NIS activity by concentration-dependent manner till 1 mM of NaI. But, the amounts of NIS mRNA were not changed, although those were transiently decreased at 24 hours after iodide treatment at the higher concentration of NaI, 10 mM or over. The amounts of NIS protein, which were analyzed by immunohistochemstry, were decreased till first 24 hours, but those were re-increased, the amounts at 48 hours after iodide treatment returned to more than 50% of basal levels. Conclusion : TSH induced the expression of NIS, while iodide inhibited the NIS activities. Our finding suggested that the excessive iodide regulates the NIS activity, at least in part, through post-translational as well as transcriptional and translational mechanisms.(Korean J Med 65:549-557, 2003)