Transforming Growth Factor-β1 Suppresses Thyrotropin-Induced Na+/I- Symporter Messenger RNA and Protein Levels in FRTL-5 Rat Thyroid Cells

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Abstract
Iodide transport into the thyroid catalyzed by the Na+/I- symporter (NIS), is the first and main rate-limiting step in thyroid hormone synthesis. Recently, we have demonstrated that thyrotropin (TSH) increases NIS messenger RNA (mRNA) and protein levels, as well as iodide uptake activity. Although transforming growth factor-β1 (TGFβ1) is known to affect thyroid cell function, it is still unclear how TGFβ1 regulates TSH-stimulated iodide accumulation. Therefore, the effects of TGFβ1 on TSH-stimulated NIS mRNA and protein levels were examined in FRTL-5 rat thyroid cells by Northern and Western blot analyses, and iodide uptake was assessed. Northern blot analysis revealed that TGFβ1 suppressed TSH-stimulated NIS mRNA levels in a dose- and time-dependent manner. Western blot analysis demonstrated that TGFβ1 suppressed TSH-stimulated NIS protein levels. TGFβ1 also suppressed (Bu)2 cyclic adenosine monophosphate (cAMP)- and forskolin-stimulated NIS mRNA and protein levels, indicating a role for TGFβ1 downstream of cAMP production. As predicted, TGFβ1 inhibited TSH-stimulated iodide uptake activity. These results suggest that the inhibitory effect of TGFβ1 on TSH-stimulated iodide uptake is at least in part due to a suppression of NIS specific transcription. Therefore, TGFβ1 may act as an autocrine or paracrine local modulator of thyroid hormone synthesis by influencing NIS mRNA levels in the thyroid.