Li Huika, Richard Kerry, McKinnon Brett, Mortimer Robin H
Department of Endocrinology, Conjoint Endocrine Laboratory, Royal Brisbane and Women's Hospital and Queensland Health Pathology Services, Brisbane, Queensland 4029, Australia.
J Clin Endocrinol Metab. 2007 Oct;92(10):4046-51. doi: 10.1210/jc.2006-2358. Epub 2007 Aug 28.
Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS.
The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by (125)I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone.
Iodide inhibited NIS mRNA and membrane protein expression as well as (125)I uptake, which were paralleled by decreased betahCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol.
We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression.
甲状腺钠碘同向转运体(NIS)介导的母体碘的主动胎盘转运为胎儿甲状腺激素合成提供了必需的底物。NIS在滋养层细胞中表达,并受人类绒毛膜促性腺激素(hCG)调节。在甲状腺中,碘可下调包括NIS在内的多个基因的表达。碘缺乏大鼠的胎盘显示NIS mRNA上调,提示碘在调节胎盘NIS中发挥作用。
目的是研究碘对BeWo绒毛膜癌细胞中NIS和hCG表达 的影响。通过定量实时PCR研究基因表达。通过蛋白质印迹法评估对NIS蛋白表达的影响。通过(125)I摄取测量NIS的功能活性。通过对分泌激素的免疫测定评估hCG蛋白的表达。
碘抑制NIS mRNA和膜蛋白表达以及(125)I摄取,同时伴随着βhCG mRNA表达和蛋白分泌的减少。碘对pendrin表达没有影响。添加hCG可增加NIS mRNA表达。添加碘可部分抑制这种作用。丙硫氧嘧啶和二硫苏糖醇可消除碘对NIS mRNA表达的抑制作用。
我们得出结论,胎盘NIS的表达受母体碘的调节。这可能是通过调节hCG对NIS和hCG基因表达的作用来实现的。