| Iodine is the essential microelement, and the primary material for thyroid to synthesize thyroid hormones. When uptaken iodine is deficient, the iodine deficiency disorders will occur. Iodine excess affects physical and mental health as well. Iodine excess could induce autoimmune thyroid disease, iodine-induced hyperthyroidism and hypothyroidism. The synthesis and secretion of thyroid hormones are recognized as a complicated process. Sodium iodide symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), pendrin and iodine are the key factors in this process. Any of them changing will affect the biological steps in the hormone synthesis. Currently, the common positive findings on the effects of chronic, long-term iodine excess on thyroid function, structure, specific genes transcription and translation are not clear-cut or available. After successfully establishing animal models of iodine deficiency and iodine excess in Wistar rats and culturing FRTL cells, we try to explore the effects of iodine on thyroid function, structure and specific genes expression. Wistar rats, weaning one month and weighting 120-140g, were randomly divided into six groups according to body weight and sex, i.e, ①low iodine(LI); ② normal iodine (NI) ; ③ five-fold iodine(5HI) ; ④ ten-fold iodine; ⑤ fifty-fold iodine(50HI);⑥one hundred-fold iodine(lOOHI). LI rats were fed with low iodine diet derived from an endemic goiter area (average iodine content in diet is 20-40μg/kg) and drank deionic water; rats in other groups were fed with normal feedstuff (average iodine content is 300-400μg/kg). Rats in NI group drank tap water,while rats in high iodine groups drank tap water containing different concentration potassium iodide: the iodine content in water was 820|ig/L<. 1845[xg/L, 10045|xg/L, 20295 fig/L respectively. Then 3 months, 6 months and 12 months later after administration, they were sacrificed. The following parameters were determined, i.e, thyroid absolute and relative wfct weight, iodine content in urine and thyroid tissue, thyroid hormones in serum and thyroid tissue, thyroid morphology, thyroid specific genes expression and immunohistochemical staining of NIS protein in thyroid.FRTL cells were passaged and cultured, then were inoculated in 25ml bottle. Incubations were performed for 24 hours, 48 hours, and 72 hours with the following agents: TSH (0.1,0.5,1.0,10,50,100mU/ml) and patassium iodide (10'6-10"3M). Using RT-PCR and Western blot, we observed the effects of TSH, iodine on specific genes expression and the expression of NIS protein at FRTL cellsResults:(1) Urine iodine in LI was significantly lower than that in NI, The iodine excess groups (HI) showed very high urinary iodine significantly, coincidental with 5,10,50,100 folds of iodine intake. Iodine in thyroid tissue in LI was obviously lower than that in NI at three months, it continuing decreased at 6 months and 12 months onwards. Thyroid tissue iodine in 5HI, 10HI, 50HI100HI were higher than that in NI at 3, 6 and 12 months, however the increased iodine content in thyroid tissues within 2 folds of iodine of NI group, not identical with the iodine intake.(2) The thyroid absolute and relative wet weight in LI were higher than those in NI at 3 months, and increased remarkably at 6 and 12 months. The histological examination of NI group indicated that the size of thyroid follicles was moderate. Epithelial cells were cubical or flat and colloid was abundant in the follicular lumen. Rats in LI demonstrated a typical goiter of iodine deficiency. The follicles were smalland the number increased obviously. The epithelial cells of thyroid follicles were significantly hyperplastic. There was little colloid in the follicular lumen. Partial follicles in 5HI and 10HI became larger and partial follicles became small. Epithelial cells were column-like. Lumen became small and colloid was a little. There was significantly hyperplasia in 50HI, 100HI,and appeared the sign of TSH-stimulating. Thyroid stereology indicated that thyroid in LI group were the small follicular hyperplasia and shaped typical goiter iodine deficiency. In iodine excess groups, especially in 50HI, 100HI, iodine excess did not induce a typical colloid goiter, but the thyroid appeard- TSH stimulating alteration. In short, the effects of iodine dificiency and iodine excess were similar, however, the shift caused by iodine deficiency was more obvious and more severe.(3) The levels of serum TIV FIV rT3 in LI were significantly lower than those in NI at 3 months, and reduced remarkably at 6 months; TTj^ FT3 reduced as well. The levels of serum TT4^ FT4> TT3> FI^ rT3 in HI decreased at both 3 months and 6 months compared with NI groups. Thyroid hormones of thyroid tissue in LI were significantly lower than those in NI at 3, 6 12 months and T3/T4 ratio was remarkably higher than that in NI. However, total T3 in HI groups were lower than that in NI, rT3 higher compared with NI, and T3/T4 ratio reduced at 3, 6, 12 months, there was no difference of T4 in thyroid tissue among NI group, iodine excess groups. These results demonstrated that either long-term iodine deficiency or iodine excess could induce hypothyroidsm, but more singnifcant in iodine deficiency rather than iodine excess.(4) TPO mRNA> NIS mRNA> PDS mRNA expressions in LI were significantly higher than those in NI groups at 3, 6, 12 months. In HI groups, NIS expression decreased from 5HI to 100HI group at 3, 6,12 months. TPO expression decreased gradually from NI to 50HI at 3 months; after rat fed for 6 months, TPO geneexpression reduced from NI to 10HI, the 50HI and 100HI groups showed increasing level compared with 10HI group. At 12 months, TPO gene expression in all HI showed increasing level than that in NI. There was no difference of Tg mRNA expression among six groups. PDS mRNA expression in HI groups showed no difference compared with that in NI group at 6 months, however, their expression increased from 5HI to 100HI than that in NI at 12 months. NIS protein in thyroid follicles increased in LI than that in NI; in HI groups, their stain density by immunohistochemistry technique decreased gradually accompanied with the increasing of iodine uptake.(5) TSH is able to stimulate the expression of NIS. TPO, TG mRNA in FRTL cells. NIS TPO Tg mRNA expressions in adding TSH groups were higher remarkably than those in control groups. When FRTL cells had been cultured in different iodide concentrations for 24 hours and 48 hours, there was no difference in NIS, TPO, Tg, PDS mRNA expressions between iodide groups and control group. However, high iodide decreased the expression of NIS protein in FRTL cells. Conclusion:(1) Iodine deficiency can give rise to obvious hypothyroidism and diffuse goiter with follicular preliferation. Long term or chronic iodine excess can also cause hypothyroidism and thyroid folliclular hyperplasia, similar to the consequence of iodine deficiency, but the degree of hypothyroidism and thyroid hyperplasia is not as far severe as iodine deficiency.(2) Wistar rats for the long-term iodine excess demonstrated the strong tolerance to iodine excess through adaptation mechanism and only chronic, long-term severe excess iodine is uptaken, hypothyroidism will occur. The adaptation mechanism may include: thyroid follicular epithelium has an auto-regulation mechanism to uptake iodide, and NIS is the important component of this autoregulation. When the uptake of iodine... |
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