Premium
Regulation of thyroid sodium‐iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species
Author(s) -
Matos Lívia P L,
Penha Ricardo Cortez Cardoso,
CardosoWeide Luciene C,
Freitas Mariana L,
Silva Diorney L S G,
Ferreira Andrea C F
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12887
Subject(s) - sodium iodide symporter , iodide , thyroid , medicine , endocrinology , symporter , chemistry , iodine , goiter , biochemistry , organic chemistry , transporter , gene
Summary Na + /I − symporter ( NIS ) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate NIS regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole ( MMI ) for 5 and 21 days, to achieve different status of goiter. We then evaluated the effect of MMI removal for 1 day (R1d), after 5 (R1d‐5d) or 21 (R1d‐21d) days of MMI treatment. MMI increased thyroid weight, iodide uptake and in vitro TPO activity in a time‐dependent way. Although MMI removal evoked a rapid normalization of TPO activity in R1d‐5d, it was still high in R1d‐21d. On the other hand, iodide uptake was rapidly down‐regulated in R1d‐21d, but not in R1d‐5d, suggesting that the increased TPO activity in R1d‐21d led to increased intraglandular organified iodine (I‐X), which is known to inhibit iodide uptake. Since TGF β has been shown to mediate some effects of I‐X, we evaluated TGF β and TGF β receptor mRNA levels, which were increased in R1d‐21d. Moreover, it has been demonstrated that TGF β stimulates NOX 4. Accordingly, our data revealed increased NOX 4 expression and H 2 O 2 generation in R1d‐21d. Finally, we evaluated the effect of H 2 O 2 on NIS function and mRNA levels in PCCL 3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and NIS regulation and that the mechanism might involve I‐X, TGF β, NOX 4 and increased ROS production.