The Expression of the Sodium/Iodide Symporter Is Up-Regulated in the Thyroid of Fetuses of Iodine-Deficient Rats

Abstract

Is the fetal thyroid already capable to increase its iodide uptake in response to iodine deficiency? To answer this question, we analyzed the expression of the Na(+)/I(-) symporter and several other genes in the thyroid of rat fetuses at 21 d of gestation from control mothers presenting a mild or more severe iodine deficiency. Female rats were placed on a low iodine diet, not supplemented, or supplemented with iodide or perchlorate for 3 months. The maternal and fetal thyroidal iodide uptake was measured 24 h after injection of 10 microCi Na (125)I into the dams. The absolute iodide uptake of the maternal thyroid was unchanged in a low iodine diet, not supplemented, compared with one supplemented with iodide. In contrast, the fetal thyroid absolute iodide uptake of a low iodine diet, not supplemented, and one supplemented with perchlorate was decreased by 70% and 95% compared with that supplemented with iodide. Na(+)/I(-) symporter mRNA was detected in the fetal thyroid of supplemented with iodide and increased about 2- and 4- fold in the thyroid of fetuses from a low iodine diet, not supplemented, and one supplemented with perchlorate, respectively. Na(+)/I(-) symporter expression was induced in the fetal side of the placenta in both a low iodine diet, not supplemented, and one supplemented with perchlorate; in contrast, Na(+)/I(-) symporter mRNA was never detected in the maternal side of the placenta. Fetal thyroid thyroglobulin and type I deiodinase mRNA contents were only significantly increased with a diet supplemented with perchlorate. Glucose transporter 4 mRNA was decreased in the fetal thyroid of both a low iodine diet, not supplemented, and one supplemented with perchlorate compared with one supplemented with iodide. In conclusion, although the up-regulation of Na(+)/I(-) symporter expression in fetal thyroid and placenta in the low iodine diet, not supplemented group did not lead to restoration of a normal absolute iodide uptake, our data show that all adaptive and/or defending mechanisms against iodine deficiency are already present in the fetus.

Na+/I− Symporter and Type 3 Iodothyronine Deiodinase Gene Expression in Amniotic Membrane and Placenta and Its Relationship to Maternal Thyroid Hormones

“…Although the distribution of NIS in the MP and the FP is not yet known in the literature, a previous study conducted on rats found NIS expression in the fetal side of placenta, but, different from our study, not in the maternal side [9]. This discrepancy between the two studies might be related to different methodologies used in these works, as immunostaining methods were used by Schroder-van der Elst et al [9]. As mentioned above, NIS expression was not detected in the different surfaces of the placenta or the amniotic membrane in some cases even though genetic material was obtained.…”

“…Our study concluded that the NIS in the amniotic membrane may contribute to iodine transmission from the mother to the fetus. Although the distribution of NIS in the MP and the FP is not yet known in the literature, a previous study conducted on rats found NIS expression in the fetal side of placenta, but, different from our study, not in the maternal side [9]. This discrepancy between the two studies might be related to different methodologies used in these works, as immunostaining methods were used by Schroder-van der Elst et al [9].…”

“…Thyroid-stimulating hormone (TSH) and iodide are two main regulators of NIS expression in the thyroid gland [5,8]. The mechanism of placental NIS expression is not yet clear, but iodide and human chorionic gonadotropin have been claimed to have a role [2,9].…”

Effects of a Dietary Thermally Oxidized Fat on Thyroid Morphology and mRNA Concentrations of Thyroidal Iodide Transporter and Thyroid Peroxidase in Rats

“…Thyrotropin is the most important regulator of thyroid hormone function. Among other functions, thyrotropin upregulates NIS and TPO [21][22][23]. Because the concentration of thyrotropin was not different between rats fed oxidized fat and those fed fresh fat, it is likely that the effect of the oxidized fat on the thyroid gland was not mediated by thyrotropin.…”

Placental Transport of Thyroid Hormone and Iodide

“…Following the discovery of NIS, persuasive evidence suggested that the inhibitory effect of iodide is associated with a decrease in NIS mRNA and protein levels, subsequently reducing iodide transport to the thyroid (Eng, et al 1999;Eng PH 2001;Glatt, et al 2005). In iodine deficient rats, NIS mRNA is up regulated in fetal thyroid, as well as in the placenta (Schroder-van der Elst, et al 2001). In BeWo cells iodide also caused a significant decrease in NIS mRNA and apical membrane protein, followed by a decrease in levels of iodide uptake (Li et al 2007).…”