Huika Li1, Kerry Richard, Brett McKinnon, Robin H Mortimer. 1. Department of Endocrinology, Conjoint Endocrine Laboratory, Royal Brisbane and Women's Hospital and Queensland Health Pathology Services, Brisbane, Queensland 4029, Australia.
Abstract
CONTEXT: 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. OBJECTIVES AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
CONTEXT: 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. OBJECTIVES AND METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Michael J Moser; Robert A DiFrancesco; Krishne Gowda; Audrey J Klingele; Darby R Sugar; Stacy Stocki; David A Mead; Thomas W Schoenfeld Journal: PLoS One Date: 2012-06-04 Impact factor: 3.240