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Iodine and the Body

 

Pregnancy

 

Filetti

 

Expression, regulation, and function of paired-box gene 8 in the human placenta and placental cancer cell lines.

Ferretti E, Arturi F, Mattei T, Scipioni A, Tell G, Tosi E, Presta I, Morisi R, Lacroix L, Gulino A, Russo D, Damante G, Filetti S.

Endocrinology. 2005 Sep;146(9):4009-15. Epub 2005 Jun 16.

 

"Pax proteins are transcriptional regulators that control a variety of developmental decisions in vertebrates. During development, the paired-box gene 8 (PAX8) is expressed in the thyroid, kidney, and several areas of the central nervous system. It is also expressed in the adult thyroid gland, in which it mediates TSH-induced modulation of the expression of important genes, such as those encoding thyroglobulin, thyroperoxidase, and the sodium/iodide symporter (NIS). Thus far, placental expression of PAX8 has been described only in mice.  In the present study, we show that PAX8 is also expressed in the human placenta at term. In an in vitro model of placental cancer, the JAR choriocarcinoma cell line, human chorionic gonadotropin (hCG) increased levels of PAX8 mRNA and protein, and gel retardation assays indicated that the up-regulation of PAX8 protein expression is associated with an increase in its DNA-binding activity. The effects of hCG were mimicked by forskolin, indicating that they are cAMP dependent. Levels of mRNA for the Wilms' tumor 1 (WT1) and NIS genes were increased in JAR cells by hCG treatment, whereas overexpression of PAX8 increased only levels of WT1 mRNA. In cells transfected with PAX8-specific small interfering RNA, the stimulatory effects of hCG on WT1 mRNA levels were abolished, but hormonal enhancement of NIS mRNA levels was unchanged. These findings indicate that, in JAR cells, hCG activates a cAMP-dependent pathway that can up-regulate WT1 expression through PAX8."

 

 

Regulation by human chorionic gonadotropin of sodium/iodide symporter gene expression in the JAr human choriocarcinoma cell line.

Arturi F, Lacroix L, Presta I, Scarpelli D, Caillou B, Schlumberger M, Russo D, Bidart JM, Filetti S.

Endocrinology. 2002 Jun;143(6):2216-20.

 

"Sodium/iodide symporter (NIS) gene and protein expressions have been recently described in human cytotrophoblasts, emphasizing its potential function in the active transport of iodide from the mother to the fetus. In this study we analyzed NIS expression and function in the human JAr placental choriocarcinoma cell line. Using real-time quantitative RT-PCR, we first demonstrated that NIS transcripts are expressed at a high level in JAr cells compared with other cell lines, including thyroid cancer cells. Functional analysis clearly showed that Jar cells are able to concentrate iodide in presence of hCG. Iodide accumulation increased after 2-h exposure to 5 IU/ml hCG, to 6-fold over the basal level after 8 h. This effect was reproduced using forskolin, the cAMP analog (Bu)(2)-cAMP, and phorbol acetate. Moreover, hCG increased both NIS mRNA after 2 h and NIS protein levels after 4 h, reaching a maximum after 8 h in both cases. In conclusion, our data demonstrate that 1) NIS is expressed in JAr cells; 2) iodide transport in JAr cells is regulated by hCG and by cAMP-dependent and -independent mechanisms; 3) the stimulation of iodide uptake is due to an increase in both NIS mRNA and protein levels; and 4) JAr cells may represent an excellent in vitro model suitable to analyze the molecular mechanisms involved in iodide transport from mother to fetus."
 

 

Expression of Na+/I- symporter and Pendred syndrome genes in trophoblast cells.

Bidart JM, Lacroix L, Evain-Brion D, Caillou B, Lazar V, Frydman R, Bellet D, Filetti S, Schlumberger M.

J Clin Endocrinol Metab. 2000 Nov;85(11):4367-72.

 

"Placental iodide transport is critical for the fetal thyroid function, but the molecular mechanisms of this transport are not understood. The expression of two recently identified iodide transporters, namely the sodium/iodide symporter (NIS) and pendrin, the product of the gene responsible for the Pendred syndrome (PDS), was studied using real-time kinetic quantitative PCR and immunohistochemistry 1) in placental tissues collected at different gestational ages and 2) in primary cultures of villous cytotrophoblast cells (VCT) that differentiate and fuse over 2-3 days in vitro to form villous syncytiotrophoblast (VSCT) cells. Both NIS and PDS genes are expressed in placenta, albeit at low levels compared with those in thyroid tissue. NIS gene expression in placental samples from first trimester and term pregnancies was similar. In contrast, the expression of PDS gene was higher in term than in first trimester pregnancy samples. In vitro, NIS gene was expressed at a high level in VCT obtained from first trimester pregnancy, and its expression decreased by 3- to 4-fold during the differentiation of VCT in VSCT. Expression of NIS was lower (up to 30-fold) in VCT obtained in placental samples from third trimester than from first trimester pregnancy. In contrast, the expression of PDS gene was low in VCT and increased by 5- to 10-fold during VSCT formation; this was observed in cells isolated from placental samples of both first trimester and term pregnancies. Immunohistochemical analysis showed that NIS protein was present on the entire membrane of VCT, whereas pendrin was mainly located at the brush border membrane of VSCT, facing the mother. In conclusion, 1) NIS and PDS genes are differently expressed in the placenta during gestation; and 2) whereas pendrin is expressed at the brush border membrane of syncytiotrophoblast cells, NIS protein is mainly located in the cytotrophoblast layer."

 

 

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