2019: Fluoride effects on deiodination in liver

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Yang H, Xing R, Liu S, Yu H, Li P - "Analysis of the protective effects of γ-aminobutyric acid during fluoride-induced hypothyroidism in male Kunming mice" Pharm Biol 57(1):29-37 (2019) doi: 10.1080/13880209.2018.1563621
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346718/

Excerpt:

The thyroid gland is highly susceptible to the effects of fluoride ions (Zeng et al. 2012), which decrease the concentration of T4. Furthermore, the liver is the main site of thyroid hormone metabolism. Therefore, we investigated the effects of GABA on thyroid hormone metabolism in the liver of hypothyroidic mice. It is well established that MCT8 is localized on the surface of the liver where it transfers T4 into hepatocytes. On the other hand, Dio1 is expressed in the liver where it catalyzes the conversion of T4 to T3 and reverse T3, and T3 to diiodothyronine (T2), which is the major source of circulating T3 (Bianco et al. 2002). Therefore, changes in the activity of Dio1 and MCT8 inevitably lead to changes in T4 and T3 levels, disrupting thyroid hormone-directed metabolism. Our results demonstrate that the expression levels of Dio1 and MCT8 increased significantly in NCG compared with the control group, indicating that fluoride improved Dio1 and MCT8 activities, promoted transmembrane deiodination of T4 and decreased T4 serum levels. These findings were consistent with previous studies (Wang et al. 2008; Haoyue et al. 2016). In theory, the increased activity of Dio1 and MCT8 lead to the enhanced conversion of T4 into T3 in the short term, this would increase serum T3 levels. However, our results indicated that fluoride treatment decreased T4 and T3 levels simultaneously. This may have occurred because fluoride ions increase Dio1 activity, which further catalyzed T3 to T2 or monoiodotyrosine, thus decreasing serum T4 and T3 levels in NCG mice. The expression levels of Dio1 and MCT8 decreased after daily treatment with 50 mg/kg of GABA and showed no significant differences in comparison to the control group. This finding indicates that GABA protects normal liver function during the metabolism of thyroid hormones by regulating Dio1 and MCT8 activity.