Low Iodine Group Research Articles

Effects of maternal iodine nutritional status on neurodevelopmental and cognitive function of rat offspring.

This study aimed to explore the effect of maternal iodine status on the brain development of offspring in rats. Since in human studies, the interference of environmental factors and other nutrients cannot be removed. A total of 48 female Wistar rats were randomly divided into four groups: low iodine (LI), normal iodine (NI), 10-fold high iodine (10HI), and 50-fold high iodine (50HI). The rats were killed on the 15th day of pregnancy and lactation after collecting 24-h urine. The iodine concentration in 24-h urine, blood, and placenta of pregnant rats, and 24-h urine, milk, blood, and mammary glands of lactating rats was determined by inductively coupled plasma mass spectrometry. The thyroid hormone of pregnant and lactating rats was detected by chemiluminescence. The offspring were subjected to the Morris water maze on the 10th day after birth. Serum was collected to detect the thyroid hormone of offspring. The protein expression of neuroendocrine-specific protein (NSP)-A and brain-derived neurotrophic factor (BDNF) in the offspring brain were studied. Iodine storage in the placenta during pregnancy and mammary glands during lactation was positively correlated with iodine intake, and iodine storage in the placenta and mammary glands in the 50HI group was significantly higher than that in the NI group (P = 0.045 and P = 0.040). Compared with the NI group, the offspring thyroid-stimulating hormone (TSH) level was significantly higher in the 10HI group (P = 0.046), and the FT4 level was significantly lower in the 50HI group (P = 0.032). The Morris water maze showed that LI and 50HI groups required longer time and distance to find the platform than the NI group (P < 0.001). The platform crossing numbers in the LI and 50HI groups decreased significantly (P < 0.001). The expression of NSP-A in offspring brain was lower in the 10HI and 50HI groups than in the NI group (P = 0.026 and P = 0,008). BDNF expression levels were significantly lower in the LI, 10HI, and 50HI groups than in the NI group (P < 0.001). Maternal iodine intake affects iodine storage in the placenta and lactating mammary gland, which in turn affects thyroid function and BDNF and NSP-A expression in the offspring.

Mechanisms of Sodium/Iodide Symporter-Mediated Mammary Gland Iodine Compensation during Lactation.

This research aimed to investigate the compensation mechanism of iodine deficiency and excess in the mammary gland during lactation. Female rats were divided into the low iodine group (LI), the normal iodine group (NI), the 10-fold high iodine group (10HI) and the 50-fold high iodine group (50HI). We measured the iodine levels in the urine, blood, milk, and mammary gland. The protein expression of sodium/iodide symporter (NIS), DPAGT1, and valosin-containing protein (VCP) in the mammary gland was also studied. The 24-hour urinary iodine concentration, serum total iodine concentration, serum non-protein-bound iodine concentration, breast milk iodine concentration, and mammary gland iodine content in the 50HI group were significantly higher than those in the NI group (p < 0.05). Compared with the NI group, NIS expression in the 50HI group significantly decreased (p < 0.05). DAPGT1 expression was significantly higher in the LI group than in the NI group (p < 0.05). The expression level of VCP was significantly increased in the 10HI and 50HI groups. In conclusion, milk iodine concentration is positively correlated with iodine intake, and the lactating mammary gland regulates the glycosylation and degradation of NIS by regulating DPAGT1 and VCP, thus regulating milk iodine level. However, the mammary gland has a limited role in compensating for iodine deficiency and excess.

Study on the Effect of Different Iodine Intake on Hippocampal Metabolism in Offspring Rats.

Iodine is an essential trace element in the human body. Severe maternal iodine deficiency during pregnancy leads to obvious intellectual disability in the offspring. The effects of iodine deficiency on brain development have been demonstrated, but there is no clear evidence of the effects of iodine excess on brain development. To clarify the effects of iodine excess on the brain development of offspring and to provide clues to the mechanisms underlying the effects of iodine deficiency and iodine excess on the brain development of offspring. In this study, animal models with different iodine intakes were constructed using potassium iodate (KIO3). The models included four experimental groups (low-iodine group one (LI, 0μg/L iodine), low-iodine group two (LII, 5μg/L iodine), high-iodine group one (HI, 3000μg/L iodine), and high-iodine group two (HII, 10000μg/L iodine)) and one control group (NI, 100μg/L iodine). There were 20 female rats in each group, and 8 offspring were chosen from each group following birth to assess metabolic alterations. The metabolites of subsets of brain hippocampal tissue were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and the results were subjected to multivariate data analysis. Differential substances were screened by t test (p<0.05), principal component analysis (PCA), and partial least squares analysis (PLS-DA, VIP>1). The thyroid function of the female rats in the experimental group was abnormally changed. Metabolic analysis showed that the five groups were separated which revealed significant differences in hippocampal tissue metabolism among the five groups of offspring. A total of 12 potential metabolites were identified, with the majority of them being related to amino acid and energy metabolism. These metabolites are involved in various metabolic pathways, are interrelated, and may play a function in brain development. Our study highlights changes in metabolites and metabolic pathways in the brain hippocampus of offspring rats with different iodine intakes compared to controls, revealing new insights into hippocampal metabolism in offspring rats and new relevant targets.

The Effects of Long-Term High Water Iodine Levels in the External Environment on the Carotid Artery

Iodine excess typically affects thyroid function in the human body and may damage carotid artery. Four investigation plots with different water iodine levels were selected in Shandong Province, China. These included a low, medium, and high iodine group and an iodine excess group whose water iodine content was < 10, 50–150, 150–300, and > 300 μg/L, respectively. Residents aged 20–65 years answered a questionnaire and underwent carotid artery ultrasonography, and their height, weight, and urinary iodine concentrations were measured. A total of 2026 individuals participated in the study. Urinary iodine concentration increased with increased water iodine levels. The medial thickening rate and intimal roughness rate in the iodine excess group were significantly higher than in the other three groups. After controlling for factors such as gender, age, and BMI, iodine excess remained as a risk factor for carotid intima-media thickening. Excess water iodine in the external environment is a risk factor for intima-media thickening of the carotid artery, suggesting that iodine excess may cause vascular injury and promote atherosclerosis.

Low urinary iodine is a protective factor of central lymph node metastasis in papillary thyroid cancer: a cross-sectional study

BackgroundAn abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients.MethodsThree hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM).ResultsThere were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(−) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31–0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21–0.87).ConclusionsLow iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens.

Thyroid damage occurs during experimental iodine-deficient goiter and involution with iodine supplementation. This study investigated the dynamic microRNAs (miRNAs) expression profiles in iodine-deficient thyroids during adequate and excessive iodine supplementation. Twenty-four female Wistar rats were randomly divided into control, low-iodine (LI), LI-1I, and LI-2I groups. The LI-1I and LI-2I groups were fed a LI diet for 12 weeks, followed by a onefold (adequate) or twofold (excessive) physiological dose of iodine for 4 weeks to induce involution. The miRNA expression profiles were evaluated and the potential functions of the differentially expressed miRNAs identified were explored. In the LI group, 20 miRNAs were downregulated and 8 were upregulated. After involution, 21 miRNAs recovered to the control group levels in the LI-1I group, which was more than the 17 that recovered in the LI-2I group. In addition, 8 new differentially expressed miRNAs were identified in the LI-1I group, which was less than the 13 found in the LI-2I group. Bioinformatics analyses indicated that all differentially expressed miRNAs were involved in different processes and pathways, such as autoimmune thyroid disease and the Ras signaling pathway. Differentially expressed miRNAs are involved in iodine-deficient goiter formation and involution. Supplementation with adequate, not excessive, iodine may be more beneficial to restore homeostasis.

Study on the relationship between hyperthyroidism and vascular endothelial cell damage

The aim of the research is to explore the relationship between hyperthyroidism, iodine, antithyroid drugs (propylthiouracil) and vascular endothelial injury. In total, 136 SD rats were randomly allocated into the control group, the hyperthyroidism group, the hyperthyroidism propylthiouracil group, the hyperthyroidism low iodine group, the high iodine group, and the endothelial injury group. Rats were raised for 60 days. Afterward, indicators concerning endothelial damage were determined, including the von Willebrand Factor (vWF), thrombomodulin (TM), nitric oxide (NO), endothelin 1 (ET-1), and P-selectin, as well as the plant hemagglutinin sample type oxidized low-density lipoprotein receptor 1 (LOX-1) from the aorta and the number of endothelial progenitor cells (EPCs) in whole blood. The hyperthyroidism group had significantly higher values for vWF, TM, NO, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with the control group, similar to the LOX-1 expression in abdominal aorta. The hyperthyroidism low iodine group had significantly higher values for vWF, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with those of the control group, as was the case for LOX-1 expression in the abdominal aorta. The hyperthyroidism propylthiouracil group had significantly higher values for FT4 in the serum compared with those in the control group. The electron microscope showed that hyperthyroidism caused a certain degree of endothelial injury to the abdominal aorta in rats. Hyperthyroidism can damage the vascular endothelium and is a high-risk factor for cardio-cerebrovascular disease. Propylthiouracil could be used in the treatment of hyperthyroidism, thus protecting endothelial cells from damage.

A PRISMA-compliant systematic review and meta-analysis of the relationship between thyroid disease and different levels of iodine intake in mainland China.

Low-iodine intake has historically been an issue in China, causing widespread iodine deficiency diseases (IDD). China started to introduce universal salt iodization in 1995, but reports of increased thyroid disease are a concern and appropriate levels of iodine intake must be considered. To assess the prevalence of thyroid disease with different urinary iodine concentrations (UICs) in the general population of those residing in mainland China. Furthermore, we aimed to analyze the relationship between thyroid disease and UIC, to provide guidance in establishing effective health policies regarding iodine intake. PubMed, Cochrane, Embase, CNKI, Wan fang, and CQVIP databases were searched for random community-based relevant studies with UIC published before January 2016 in mainland China. Two independent reviewers extracted data from eligible citations, and obtained prevalence of thyroid disease for different UICs, as well as the intergroup interaction P values. Forty-three articles were included. The prevalence of thyroid nodules was 22.3% (95% confidence interval [CI]: 20.6%-24.1%) for the low-iodine group, 25.4% (95% CI: 20.8%-28.8%) for the medium-iodine group, and 6.8% (95% CI: 2.8%-11.5%) for the high-iodine group. In the high-iodine group, the prevalence of thyroid nodules was lower than the other groups. The prevalence of 8.3% (95% CI: 3.8%-17.3%) for subclinical hypothyroidism in the high-iodine group was significantly higher than the low- and medium-iodine groups (P < .01). The prevalence of hypothyroidism in the medium-iodine group was 0.2% (95% CI: 0.1%-0.4%), and was lower than the prevalence of the other 2 groups (P < .01). There was no difference in prevalence of hyperthyroidism in each group. Thyroid nodules are the most easily detectable thyroid disease. These have a lower prevalence in the high-iodine group. The prevalence of most thyroid diseases is lowest for a UIC ranging from 100 to 299 μg/L. This serves as a reference for health policy-making with respect to iodine levels. Further studies on this topic should be carried out according to sufficient thyroid cancer data.

Long-term effect of iodine deficiency on growth and food utilization rate in second filial generation rats

Objective: To study the effect of iodine deficiency on body weight, food consumption, and food utilization rate of second filial generation Wistar rats. Methods: According to the food pattern of a high-iodine deficient population, two types of low-iodine food have been produced using the main crops grown in this area (iodine levels of 50 and 20 μg/kg, respectively). Wistar rats were randomly divided into three groups, normal iodine group (NI group), low-iodine group one (LI group) and low-iodine group two (LII group), using the random number table method and fed diets containing 300, 50, and 20 μg/kg of iodine, respectively. Parental generation rats were fed until they reached reproductive age; first filial generation rats were allocated to the same diet as their mothers. After 3 months of feeding, first filial generation rats gave birth to second filial generation rats; second filial generation rats were allocated to the same diet as their mothers. After feeding for 90, 180, and 270 days, rats were sacrificed. One-way analysis of variance was used to analyze body weight, food intake, and food utilization rate data collected during the time of feeding and blood iodine hormone level, which was determined after sacrifice. Results: The LI and LII groups generally demonstrated decreased activity, slow reaction, and growth retardation compared with the NI group. After 270 days, the urine iodine levels of the LI and LII groups were 1.7 and 0.2 μg/L, respectively, which were significantly lower than the NI group (255.2 μg/L) (P<0.001). Additionally, the weight of female rats in the LI and LII groups were (288.1±10.5) and (275.7±2.7) g, respectively, which was significantly lower than that of the NI group ((311.0±2.3) g) (P<0.001). The weight of male rats were (446.0±4.6) and (451.8±19.1) g, respectively, which were significantly lower than that of the NI group ((517.2±7.8) g) (P<0.001). In the LI and LII groups, food intake of female and male rats after 270 days were (465.0±27.7), (658.4±28.6) and (423.0±13.2), (548.0±18.8) g, respectively, which were significantly lower than that of the NI group ((499.5±21.8), (760.8±33.0) g) (P<0.001). Moreover, the food utilization rate of female rats in the LI and LII groups was (8.7±0.4)% and (6.0±0.58)%, which was lower than that of the NI group ((11.7±3.5)%) (P<0.001); similarly, male rats showed rates of (8.9±1.5)% and (6.9±1.31)%, respectively, which were lower than that of the NI group ((13.7±3.0)%) (P<0.001). After 270 days, the level of T3 in the LI and LII groups were (0.45±0.10) and (0.34±0.15) ng/ml, respectively, which was significantly lower than that of the NI group ((0.91±0.49) ng/ml) (P<0.01). Moreover, the level of T4 were (69.02±27.87) , (53.18±13.53) ng/ml in LI and LII groups, respectively, which was lower than that of the NI group ((76.69±29.42) ng/ml) (P<0.05). Conclusion: This study indicated that iodine deficiency induced by a long-term low-iodine diet can cause changes in weight, food intake, and food utilization rate among second filial iodine deficiency rats. More importantly, the iodine content in low-iodine food impacts these parameters.

High-pitch, low-voltage and low-iodine-concentration CT angiography of aorta: assessment of image quality and radiation dose with iterative reconstruction.

ObjectiveTo assess the image quality of aorta obtained by dual-source computed tomography angiography (DSCTA), performed with high pitch, low tube voltage, and low iodine concentration contrast medium (CM) with images reconstructed using iterative reconstruction (IR).MethodsOne hundred patients randomly allocated to receive one of two types of CM underwent DSCTA with the electrocardiogram-triggered Flash protocol. In the low-iodine group, 50 patients received CM containing 270 mg I/mL and were scanned at low tube voltage (100 kVp). In the high-iodine CM group, 50 patients received CM containing 370 mg I/mL and were scanned at the tube voltage (120 kVp). The filtered back projection (FBP) algorithm was used for reconstruction in both groups. In addition, the IR algorithm was used in the low-iodine group. Image quality of the aorta was analyzed subjectively by a 3-point grading scale and objectively by measuring the CT attenuation in terms of the signal- and contrast-to-noise ratios (SNR and CNR, respectively). Radiation and CM doses were compared.ResultsThe CT attenuation, subjective image quality assessment, SNR, and CNR of various aortic regions of interest did not differ significantly between two groups. In the low-iodine group, images reconstructed by FBP and IR demonstrated significant differences in image noise, SNR, and CNR (p<0.05). The low-iodine group resulted in 34.3% less radiation (4.4 ± 0.5 mSv) than the high-iodine group (6.7 ± 0.6 mSv), and 27.3% less iodine weight (20.36 ± 2.65 g) than the high-iodine group (28 ± 1.98 g). Observers exhibited excellent agreement on the aortic image quality scores (κ = 0.904).ConclusionsCT images of aorta could be obtained within 2 s by using a DSCT Flash protocol with low tube voltage, IR, and low-iodine-concentration CM. Appropriate contrast enhancement was achieved while maintaining good image quality and decreasing the radiation and iodine doses.

Iodine deficiency up-regulates monocarboxylate transporter 8 expression of mouse thyroid gland

Background Iodine deficiency is a major factor affecting thyroid auto-regulation, the quantity of iodine may greatly influence the synthesis of thyroid hormones (THs). It has long been believed that TH enters the cell through passive diffusion. Recent studies have suggested that several transporters could facilitate transportation of TH. The monocarboxylate transporter 8 (MCT8) was identified as a very active and specific TH transporter. The purpose of this study was to investigate whether iodine insufficient affected the expression of MCT8 in the thyroid gland. Methods Sixty BALB/c mice were randomly divided into two groups: control group was fed with standard feed (iodine concentration of 300 μg/kg); while low-iodine (LI) group received iodine-insufficient feed (iodine concentration of 20-40 μg/kg). After 3 months, 10 mice of each group were sacrificed. The remaining 20 mice of each group were kept till 6 months. From the LI group, we randomly selected 15 mice and injected triiodothyronine (T3, 100 μg/kg body weight per day) intraperitoneally for 24, 48 or 72 hours (5 mice for each time-point). Then, all the mice were sacrificed. Mouse serum thyroxine (T4), T3, and thyroid-stimulating hormone (TSH) levels were determined by chemiluminescence immunoassay (CIA). The protein content or messenger RNA (mRNA) level of thyroid MCT8 was measured by Western blotting analysis or real time RT-PCR respectively. MCT8 subcellular location in thyroid tissues was probed with immunohistochemistry (IHC) assay. Results We found that mouse serum T3 and T4 levels decreased and TSH level increased by the end of the third month. Consistent with these findings, there was significant goiter and hypothyroidism in the LI group. Meanwhile, the MCT8 mRNA increased to 1.36-fold of the level in the control group at the 3rd month. At 6th month, the serum T4 level in LI mice remained at a lower level, and MCT8 mRNA expression continued rising to nearly 1.60-fold compared with the control group. The protein content was also about 3 times higher than that in the control group. IHC results also revealed MCT8 was of higher expression and localized in the cytoplasm of thyroid follicular cells. After providing exogenous T3 to iodine deficient mice, the serum T3 and T4 gradually increased, whereas MCT8 mRNA and protein both started to decrease and returned to the same level as the control group. Conclusion There is a compensatory increase in thyroid MCT8 expression to enhance its capability to transport TH from thyroid to the blood circulation in iodine deficient mice.

Effects of High Fluoride and Low Iodine on Thyroid Function in Offspring Rats

Thirty-two Wistar rats were divided randomly into four groups of eight with six females and two males in each group. The rats were exposed to high fluoride drinking water (45 mg F− L−1 from 100 mg NaF L−1), low dietary iodine (0.0855 mg kg−1), or both together in order to assess the effects of these three regimens on the thyroid function of the offspring rats. After the animal model was established, the offspring rats were bred and 10-, 20-, 30-, 60-, and 90-d-old rats were used for the experiment. The treatments for the offspring rats were the same as those of their parents. In comparison with control rats, the relative thyroid glands were changed by three regimens, but the mean values of thyroid weight in the experimental groups saw no marked difference. Serum TT3 levels were increased in all stages in the low iodine (LI) group. In the high fluoride (HiF) group, increase in TT3 levels was observed except in 20-d-old rats. Decrease in TT3 at 20- and 90-d and increase in TT3 at 30- and 60-d were found in HiF+LI group. Serum TT4 levels first saw an increase, and then dropped in the LI and HiF+LI group. However, an increase in TT4 was found in the HiF group. The levels of TSH in serum rocketed at d 20, and then dropped in the next stages in experimental groups. The results suggested that thyroid disorder could be induced by high flroride in drinking water, low iodine diet, or both of them. Exposure time to fluoride or low iodine diet was one of the important factors that fluoride can induce the development of thyroid dyfunction.

Effect of dietary iodine on thyroid hormones and energy blood metabolites in lactating goats

Aim of this work was to evaluate if long-term dietary supplementation of potassium iodide (KI) to dairy goats can influence metabolic and hormonal parameters. Thirty Sarda crossbred dairy goats were divided into three groups, which were orally administered 0 (control group; CON), 0.45 (low iodine group; LI) or 0.90 (high iodine group; HI) mg of KI/day, respectively. The daily dose of KI (76.5% of iodine) was administered as salt dissolved in water for 8 weeks. Plasma contents of nonesterified fatty acids (NEFA), urea, glucose, insulin, free triiodothyronine (FT3) and thyroxine (FT4) were determined weekly. Iodine supplementation increased significantly the FT3 hormone (P = 0.007) and FT3/FT4 ratio (P = 0.001) and tended to influence the FT4 hormone (P = 0.059). An iodine level × week of sampling interaction for NEFA (P = 0.013) evidenced a temporary concentration increase in supplemented groups. The ‘Revised Quantitative Insulin Sensitivity Check Index’ increased with KI supplementation (P ⩽ 0.01). Blood urea nitrogen (BUN) and insulin were lowered (P ⩽ 0.01) by iodine supplementation (groups LI and HI; P ⩽ 0.01). The glucose concentration evidenced an iodine level × week of sampling interaction (P = 0.025) due to an unexpected and temporary increase of its concentration in the CON group. Glucose concentration was decreased by KI supplementation only in LI group (P < 0.05). In conclusion, the daily supplementation of low doses of KI can improve insulin sensitivity and decrease BUN in dairy goats.

Changes of Sodium Iodide Symporter Regulated by IGF-I and TGF-β1 in Mammary Gland Cells from Lactating Mice at Different Iodine Levels

The sodium/iodide symporter (SLC5A5, also known as NIS) is a transmembrane glycoprotein. Physiologically, iodide transportation in the mammary gland occurs during late pregnancy and lactation. To identify factors that may regulate this process at different iodine levels, we have studied the expression of NIS gene and protein in cultured mammary gland explants from lactating mice by real-time quantitative PCR and In-Cell Western methods. Mammary gland cells were grown in media with different levels of iodine for 24h. The iodine treatment groups consist of low iodine group I (LI-I, 0μg/l), low iodine group II (LI-II, 5μg/l), control group (C, 50μg/l), high iodine group I (HI-I, 3,000μg/l), and high iodine group II (HI-II, 10,000μg/l). The cells were then incubated with or without insulin-like growth factor I (IGF-I) or transforming growth factor β1 (TGF-β1) for another 24h. We found that iodine inhibited NIS mRNA and protein expression in a dose-dependent manner. IGF-I and TGF-β1 further decreased NIS mRNA and protein expression that iodine inhibited at different iodine levels. In summary, we have shown that iodine downregulated NIS expression in cultured mammary gland explants from the lactating mouse. IGF-I and TGF-β1 inhibited NIS mRNA and protein expression in the mammary gland under different iodine levels.

Effects of low-iodine diet on the expression of homeobox gene NKX-6.1 and NKX-6.2 in rat cerebrum tissue

Objective To study the influence of low-iodine diet on the expression of homeobox gene Nkx-6.1 and Nkx-6.2 in rat cerebrum tissue, and to explore the possible molecular mechanism of cerebrum development retardation caused by low-iodine. Methods Twenty female Wistar rats were randomly equally divided into two groups: low-iodine group and control group, both fed with low-iodine diet as low as 13.66 μg/kg determinated by spectrophotometry in Tianjin Institute of Endocrinology and the former with deionized water, the later 200 μg/L potassium iodate. Thyroid hormone level was detected using chemiluminescence immunoassay 3 months later and they were mated with male rats normally fed. Rats of 16-day pregnancy, new-born and 20th days old were detected the content of Nkx-6.1 and Nkx-6.2 mRNA in the cerebrum tissue by real-time fluorescence quantitative PCR 0.61), (3.28±0.80)pmol/L] were lower than the control group[(1.04±0.06), (39.42±14.68)nmol/L, (4.83±0.33), day pregnancy, new-born and 20th days old of control group was (1.90±0.23)×10-3,(1.86±0.40)×10-4, (1.11± 0.27)×10-4(F=827.58, P<0.01), Nkx-6.1 mRNA expression level gradually decreased along with aging(all P<0.05). The intra-group difference was significant (F=297.25, P<0.01) and the Nkxr.1 mRNA expression level during 16 days of pregnancy was the highest(P<0.01). It was higher in the control group than in the low-iodine group during 16 days of pregnancy (t=10.14, P<0.01) as well as in the low-iodine group than in the in 16-day pregnancy, new-born and 20th days old of control group was respectively(1.03±0.19)×10-2, (1.33± 0.10)×10-3, (8.79±0,87)×10-3, and that of low-iodine group was (0.31±0.03)×10-2, (1.53±0.13)×10-3, (7.51±0.86)×10-2. The intra-group difference was significant(F=1293.02,1065.83, all P<0.01). Nkx-6.2 expression level during 20th days old was the highest(P<0.01) and that of newborn was the lowest(P<0.01). The Nkx6.2 mRNA expression level in control group were higher than the low-iodine group during 16-day pregnancy and 20th days old(t=14.35, 4.05, all P<0.01). It was higher in the low-iodine group than in the control group during newboru(t=4.78, P<0.01). Conclusions The difference in the expression of Nkx-6.1 and Nkx-62 is highly related to the brain development retardation caused by low-iodine. Key words: Genes; homeobox; Polymerase chain reaction; Developmental disabilities; brain

Sodium iodide symporter gene expression in thyroid of mice with different iodine intakes

Objective To investigate the sodium iodide symporter (NIS) gene expression during different iodine intakes and its function in thyroid autoregulation. Methods BabL/c mice were randomly divided into five groups according to their different iodine intake levels : low iodine (LI), normal iodine (NI), five-fold iodine (5HI) ,ten-fold iodine (10 HI) and fifty-fold iodine (50 HI). After three months and six months administration, they were sacrificed and thyroids were excised. The mRNA and protein expression level were determined by real time quantitative PCR and immunohistochemistry respectively. Iodine content in thyroid tissue was measured with spectrophotometry and thyroid hormone level was measured with radioimmunoassay. Results Compared with NI group, NIS mRNA and protein expression was greatly increased in LI groups. Immunohistochemistry analysis indicated that NIS was mostly located at the basolateral membrane of thyrocyte,suggesting the improved activity in transporting iodine. But when faced with long-term and severe iodine deficiency, the iodine content in thyroid was finally decreased ,and hormone level lowered. On the other hand, in HI groups NIS mRNA and protein expression was greatly down-regulated. There was a tendency of decreasing NIS gene expression level with increasing doses of iodine intakes. In addition, NIS protein was found mainly in intracellular vesicles, rather than at the cell membrane,suggesting the loss of its activity. The iodine content in thyroid tissue was only slightly increased and was not consistent with the iodine intake levels. Conclusion These findings indicate that NIS may be. regulated at transcription, translation and post-translation levels. This phenomenon constitutes a highly specialized intrinsic autoregulatory system that protects thyroid from high doses of iodine, but at the same time ensures adequate iodine uptake for hormone biosynthesis. NIS plays a critical role in thyroid autoregulation mechanism. Key words: Sodium iodide symporter; Gene expression; Thyroid hormone; Iodine deficiency; Iodine excess

The effects of iodine/selenium on the function of antigen presentation of peritoneal macrophages in rats

To observe the effects of iodine/selenium on the function of antigen presentation of peritoneal macrophages in rats and explore the immunological mechanisms of iodine/ selenium's role in pathogenesis of autoimmune thyroid diseases (AITD). Female Lewis rats were randomly divided into four groups including (1) low selenium and normal iodine group (L(sE)N(I)) (2) low selenium and high iodine group (L(Se)H(I)) (3) normal selenium and normal iodine group (N(Se)N(I) ) (4) normal selenium and high iodine group (N(Se)H(I)). All rats were fed by a special diet with lower selenium and iodine in it and drunk ion-free water containing different levels of iodine and selenium for 3 months. Peritoneal macrophages of each group and OVA allergized T cells were prepared and cultured together. Then the function of antigen presentation were estimated by detecting the levels of IL-2 in the culture supernatant. The levels of the expression of co-stimulator CD86 in the spleen of each group were determined by RT-PCR. The level of IL-2 in the supernatant in N(Se)H(I) (43.22 +/- 3.27) pg/ml was much stronger than N(Se)N(I) [the level of IL-2 was (25.74 +/- 2.45) pg/ml, P < 0.05]. The level of IL-2 in L(Se)N(I) (15.79 +/- 2.13) pg/ml was significantly lower than N(Se)N(I) (P < 0.05). The expression of CD86 mRNA in N(Se)H(I) (CD86/beta-actin: 0.52 +/- 0.10) were higher than N(Se)N(I) (CD86/beta-actin: 0.35 +/- 0.04), P < 0.05. High iodine could promote the presentation function of macrophages to a higher state than normal. Therefore, high iodine intake might become an importantly inducing factor in thyroid autoimmunity. Low selenium could weaken the ability of recognizing and presenting OVA antigen of peritoneal macrophages which might destroy immunological homeostasis and thus the low selenium intake might also become an inducer of AITD.

Thyroid Alert: Low Iodine and Perchlorate Effects in Women

Vol. 114, No. 12 EnvironewsOpen AccessThyroid Alert: Low Iodine and Perchlorate Effects in Womenis accompanied byUrinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the United States Richard Dahl Richard Dahl Search for more papers by this author Published:1 December 2006https://doi.org/10.1289/ehp.114-a714aAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Perchlorate, an oxidizer in solid rocket fuel, is widely found in groundwater, drinking water, milk, vegetables, fruit, grain, and forage crops. Large doses of perchlorate have been shown to inhibit iodide uptake and reduce thyroid hormone production, which can contribute to metabolic problems in adults and abnormal neurodevelopment during gestation and infancy. Now, researchers at the CDC show that U.S. women with low iodine intake may be at risk for reduced thyroid function due to perchlorate exposure [EHP 114:1865–1871; Blount et al.].The researchers examined 2,299 men and women, aged 12 and older, who participated in the National Health and Nutrition Examination Survey. Examining the relationship between urine perchlorate concentrations and blood levels of the thyroid hormones thyroxine (T4) and thyroid-stimulating hormone (TSH), which stimulates T4, they observed that perchlorate was a significant predictor of thyroid hormone levels in women, but not in men.Upon seeing this sex-based difference, the authors then categorized 1,111 women into “sufficient” and “low” iodine groups using a threshold of 100 μg/L urinary iodine, based on WHO recommendations. They found a slight relationship between perchlorate concentrations and TSH for the sufficient-iodine group, but a much stronger one for perchlorate and both T4 and TSH in the low-iodine group.For the low-iodine group, higher perchlorate was associated with lower serum T4 and higher TSH. This relationship was consistent with what would be expected if perchlorate were inhibiting iodine uptake to such an extent that it interfered with thyroid hormone production. At the 50th percentile of urinary perchlorate (2.9 μg/L), the predicted decrease in T4 was 1.06 μg/dL; at the 95th percentile (13 μg/L), the predicted decrease in T4 was 1.64 μg/dL. Given that the normal range of T4 for women is 5–12 μg/dL, these predicted reductions were significant and indicate that even small increases in perchlorate exposure may inhibit the thyroid’s ability to absorb iodine.In the United States, 36% of women have urinary iodine levels under 100 μg/L. In addition, the perchlorate doses seen to cause effects in this study are well below the 24.5 ppb reference dose recommended in 2005 by a National Academy of Sciences panel. The authors say that another large study is needed to confirm these findings; they are planning that study.One thing leads to anotherThyroid tissue, with thyroglobulin, a protein used to produce T4, shown in orange. Perchlorate may interfere with iodide uptake by the thyroid, leading to altered thyroid hormone synthesis.FiguresReferencesRelatedDetailsRelated articlesUrinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the United States5 October 2006Environmental Health Perspectives Vol. 114, No. 12 December 2006Metrics About Article Metrics Publication History Originally published1 December 2006Published in print1 December 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Type 1 iodothyronine deiodinase activity and mRNA expression in rat thyroid tissue with different iodine intakes

Type 1 deiodinase (D1) plays an important role in the metabolism of thyroid hormone and has close relationship with thyroid function. In this study we explore the effects of iodine intake on D1 activity and its mRNA expression and its possible mechanism. Forty-eight Wistar rats were randomly divided into six groups with 8 in each: low iodine (LI), normal iodine (NI), five-fold iodine (HI(5)), ten-fold iodine (HI(10)), fifty-fold iodine (HI(50)), one hundred-fold iodine (HI(100)) group. Three months, six months and twelve months after admistration of potassium iodate, they were sacrificed and thyroids were excised. The expression of D1 mRNA in the thyroid tissue was determined by RT-PCR and D1 activity was analyzed by (125)I-rT3 as substrate. The thyroid hormone was measured with radioimmunoassay method. Compared with NI group, D1 mRNA expression in LI groups slightly decreased, and D1 activity greatly increased. Both T(3) and T(4) in thyroid tissue significantly decreased, but the T(3)/T(4) ratio increased. D1 mRNA expression decreased in all HI groups, and D1 activity was significantly lower in HI groups. There was a tendency of decrease in D1 activity with increased doses of iodine intakes. There was no significant difference in T(4) in thyroid tissue between HI groups and NI group, but a tendency of decrease in T(3) level was found in all HI groups. In the case of iodine deficiency, D1 activity increased greatly in order to convert more T(4) to T(3). Excess iodine can inhibit both D1 mRNA expression and its activity to protect organism from being injured by excessive T(3).

Iodine status in vegans consuming a living food diet

The dietary intake and urinary output of iodine and the thyroid activity was measured in 12 living food eaters (people consuming uncooked, Lactobacilli rich vegan food) and omnivores. Seven day food record was used for calculating the dietary iodine intake, instrumental neutron activation analysis for measuring the urinary iodine output and RIA for determining of the thyroid hormones (TSH and FT4). The living food eaters were divided into two groups according to urinary iodine output: high iodine group (≥900 ug/d) and low iodine group (<200 ug/d). Thyroid activity in both groups was with in normal range. Dietary intake of iodine was dependent on the the use of seaweed. The highest amounts of dietary iodine observed in the present study, as assessed by the the urinary iodine output, can be harmful for susceptible subjects. On the other hand the calculated intake of iodine by living food eaters didn't fill the RDA. As an conclusion on a living food diet one has to ensure the sufficient intake of iodine by consuming seaweed or Kelp tablets daily. However the intake of these preparations needs to be kept at reasonble limits due to their possible high iodine content. More information of the iodine content of different seaweeds and seaweed products is needed.