Transforming Growth Factor-β 1 Suppresses Thyrotropin-Induced Na + /I - Symporter Messenger RNA and Protein Levels in FRTL-5 Rat Thyroid Cells

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.