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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF Expression in the Rat Fetal Brain Following Maternal Hypothyroidism.

To investigate the mechanism responsible for the neurological alterations, miRNA expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in brain tissues of fetal or neonatal rats and from maternal rats with hypothyroidism. Ninety female Wistar rats were divided into a control and a hypothyroid group, which were mated. Brain samples of the offspring were obtained at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7, and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested by real-time PCR and protein expression by Western blot. Luciferase assays were used to confirm that miR-206 targets the 3'-untranslated region (3'-UTR) of BDNF. In the brain tissues of fetal and neonatal rats from maternal rats with hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and P7. Compared with the control group, miR-206 levels in the hypothyroidism group were increased by 3.1-fold by micro-array, and were higher as measured by SYBR green real-time qRT-PCR (p<0.01). There was no significant difference in the BDNF mRNA levels at E13 between the hypothyroidism group and the control group (1.767±0.477 vs. 1.798±0.462, respectively; p>0.05), but pro-BDNF and mature BDNF protein levels in the hypothyroid group at E13 were significantly lower than those in the control group (p<0.05). miR-206 targeted 3'-UTR of BDNF. Our data highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13 in pregnant hypothyroid rats.

An epidemiological study of the serum thyrotropin reference range and factors that influence serum thyrotropin levels in iodine sufficient areas of China.

The aims of this study performed in 2007 were to verify the selection criteria proposed by the National Academy of Clinical Biochemistry (NACB) guidelines, to investigate factors that influence thyrotropin (TSH) levels, and to determine serum TSH reference range in iodine sufficient areas of China. After excluding 291 subjects, a total of 5,348 inhabitants from three iodine sufficient areas of Liaoning province were asked to fulfill the questionnaire, and take TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) measurements and a thyroid ultrasound examination. The distribution of TSH was right skewed in normal people. It has been customary to log transform the values to observe the Gaussian distribution. In the subjects 12-19 years of age, the TSH level was significantly higher than in the other age groups (p<0.001), while there were no significant difference in the TSH values of the other age groups. The TSH levels in females(1.68±1.90mIU/L) were significantly higher than in males (1.45±1.92mIU/L) (p<0.001). Therefore, the normal TSH range in males over age 20 was 0.43-4.74mIU/L, and in females the range was 0.48-5.39 mIU/L. A family history of thyroid disease, abnormal thyroid ultrasound, a thyroid antibody-positive status were the factors that influenced the TSH reference range. Non-thyroid disease did not impact the TSH reference range significantly. We recommend use of a TSH reference range 0.46-5.19mIU/L in iodine sufficient areas of China for males and females over 20 years old. We suggest using a normal thyroid ultrasound as a new criterion in addition to the NACB guidelines to determine the TSH reference range.

Vitamin E ameliorates iodine-induced cytotoxicity in thyroid.

Acute and excessive iodine supplementation leads to iodine-induced thyroid cytotoxicity. Excessive oxidative stress has been suggested to be one of the underlying mechanisms in the development of thyroid cytotoxicity. The aim of this study was to investigate whether vitamin E (VE), an important antioxidant, could ameliorate iodine-induced thyroid cytotoxicity. A goiter was induced in rats by feeding a low-iodine (LI) diet for 12 weeks. Involution of hyperplasia was obtained by administering a twofold physiological dose of iodine in feeding water with/without the supplementation of 25-, 50-, or 100-fold physiological dose of VE in the LI diet for 4 weeks. In iodine-supplemented rats, thyroid epithelial cell ultrastructure injuries remained and were more severe. Relative weights of iodine-induced involuting glands were significantly reduced compared with the goiter, but still higher than control. Immunohistochemistry indicated that the expression of 4-hydroxynonenal, 8-hydroxyguanine, peroxiredoxin 5, and CD68 in thyroid increased (P<0.01), whereas thioredoxin reductase 1 decreased (P<0.01). VE supplementation attenuated thyroid cytotoxicity induced by iodine. A 50-fold VE dose was optimal in attenuating twofold iodine-induced thyroid cytotoxicity. However, VE supplementation did not reduce the weight or relative weight of the iodine-induced involuting gland. These results show that excess iodine leads to thyroid damage and VE supplementation can partly ameliorate iodine-induced thyroid cytotoxicity.

More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels.

OBJECTIVE: With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200-300 µg/l) or excessive iodine intake levels (MUI >300 µg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations. DESIGN: A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 µg/l; Chengshan, MUI 145 µg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant. RESULTS: The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P<0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, P=0.02; TgAb: 10.27 vs 7.93%, P=0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: ≥500 IU/ml) and low concentrations of TgAb (TgAb: 40-99 IU/ml) in Rongxing. CONCLUSIONS: More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations.

The correlation between thyrotropin and dyslipidemia in a population-based study.

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity.

The relationship between serum thyrotropin and components of metabolic syndrome.

To explore the relationship between serum thyrotropin and components of metabolic syndrome in a Chinese cohort. A total of 1534 adult inhabitants in DaDong district of Shenyang were asked to fulfill the questionnaire, complete physical examination and OGTT. Blood samples were collected to test thyrotropin (TSH), fasting plasma glucose (FPG), OGTT 2h PG, fasting insulin (FINS), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C). Serum TSH in metabolic syndrome group was higher than that in the non-metabolic syndrome group (2.54 mIU/L vs. 2.22 mIU/L, p<0.05). TG level increased significantly in subclinical hypothyroid group compared with euthyroid subjects (1.73±0.12 mmol/L vs. 1.47±0.03 mmol/L, p<0.05), and HDL-C decreased significantly in patients with subclinical hypothyroidism compared with euthyroid subjects (1.26±0.27 mmol/L vs. 1.33±0.27 mmol/L, p<0.05). The prevalence of hypertension was higher in the subclinical hypothyroid group than that in euthyroid group (42.86% vs. 33.2%, p<0.05). The serum TSH within the reference range was positively related with the prevalence of overweight/obesity. Slight increase in serum TSH maybe a risk factor for metabolic syndrome.