The Effect Of Iodine On The Activity And MRNA Expression Of Type 2 Iodothyronine Deiodinase In Central Nervous System Of Mice

Object: Based on successful establishment of animal models of iodinedeficiency and iodine excess in BALB/C mice, we measured thebrain type2 iodothyronine deiodinase(D2) activity and its mRNA expression toinvestigate the effects of iodine on central nervous system.Methods: We selected the healthy BALB/C mice for our animal models, theywere devided into 5 groups: low iodine (LI), normal iodine (NI), five-foldiodine (HI₅), ten-fold iodine (HI₁₀), fifty-fold iodine (HI₅₀) group. LImice were fed with low iodine diet (average iodine content is 20-50μg/kg)and drank deionic water. Mice in other groups were fed with normalfeedstuff (average iodine content is 300-400μg/kg). Mice in NI groupdrank deionic water (average iodine content is 0μg/kg), whereas mice inhigh iodine groups drank deionic water containing differentconcentration of potassium iodide(5 times, 10 times, 50 times iodinerespectively). Three months and six months after admistration ofpotassium iodide, the level of urine iodine was analyzed by usingperoxodisulfuric acid amine digest -arsenic and cerium catalyzespectrophotometric method, then they were sacrificed and cerebrum,cerebellum and hippocampus were excised, the following indicators weremeasured: the level of thyroid hormones was analyzed by using Bayerchemoluminescence method. D2 activity was analyzed by ion exchangechromatography and the expression of D2 mRNA of different encephalic region was determined by Real-time RT-PCR.Results:(1) Urinary iodine: The urinary iodine level in LI group was very low,and the urinary iodine level in NI and all HI groups were significantlyparlleled with their iodine intakes of 5, 10, 50 folds. The relativityof these two was excellent (r=0.96), animal model was successful.(2) TH level: In 3 months study, serum T₄, FT₄ of LI group decreasedsignificantly compared to NI group (P＜0.01), all of the HI groupsincreased, only the FT₄ of HI₁₀ group significantly increased (P＜0.05).The T₃ and FT₃ of 3 months.increased in LI group, decreased in all HIgroups, T₃ of HI₅, HI₁₀ and HI₅₀ group, FT₃ of HI₁₀ and HI₅₀ decreasedsignificantly (P＜0.05); In 6 months study, T₄, FT₄, T₃ and FT₃ of LI groupwere lower than NI group (P＜0.05), T₄, FT₄, T₃ and FT₃ in HI₅ group, FT₄,T₃ and FT₃ in HI₁₀ group and FT₃ of HI₅₀ group increased significantly (P＜0.05). The increase of TH in HI₅ group was much more significant.(3) The D2 activity of mice in different groups: Compared with NI group,D2 activity was significantly higher in LI groups and lower in HI groupsat 3 and 6 months (P＜0.05). There was a tendency of decrease in D2activity with increased doses of iodine intakes, but there was nosignificant difference compared to NI group.(4) The D2 mRNA expression of cerebrum, cerebellum and hippocampusof mice in different groups: Compared with NI group, the D2 mRNAexpression of cerebrum increased in LI group at 3 and 6 months anddecreased significantly in HI₅ group at 6 months, and there was nosignificant difference in other groups; The D2 mRNA expression of cerebellum was significantly higher in LI group at 3 months and lowerin HI₅ group at 6 months; The D2 mRNA expression of hippocampus wassignificantly higher in LI group at 3 months and lower in HI₅ and HI₁₀ groupat 6 months, and there was no significant difference in other groups.Conclusions: Through the index as described above, we could get theseconclusions as follows: Iodine deficiency could induce hypothyroidism,in the case of iodine excess, the TH level decreased or get close to thenormal level, this explained that the tolerance of body to iodine excesswas lagerer than to iodine dificiency. In the case of iodine deficiency,D2 activity and mRNA expression decrease to convert more T₄ to T₃, whereasin the case of iodine excess, D2 activity and mRNA expression wereinhibited to protect organism from being injured by excessive T₃.