TRANSFORMING GROWTH FACTOR-BETA(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 (N IS), is the first and main rate-limiting step in thyroid hormone synth esis. 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-beta(1) (TGF beta(1)) is known to affect thyroid cell function, it is still unclear how TGF be ta(1) regulates TSH-stimulated iodide accumulation. Therefore, the eff ects of TGF beta(1) on TSH-stimulated NIS mRNA and protein levels were examined in FRTL-5 rat thyroid cells by Northern and Western blot ana lyses, and iodide uptake was assessed. Northern blot analysis revealed that TGF beta(1) suppressed TSH-stimulated NIS mRNA levels in a dose- and time-dependent manner. Western blot analysis demonstrated that TGF beta(1) suppressed TSH-stimulated NIS protein levels. TGF beta(1) als o suppressed (Bu)2 cyclic adenosine monophosphate (cAMP)- and forskoli n-stimulated NIS mRNA and protein levels, indicating a role for TGF be ta(1) downstream of cAMP production. As predicted, TGF beta(1) inhibit ed TSH-stimulated iodide uptake activity. These results suggest that t he inhibitory effect of TGF beta(1) on TSH-stimulated iodide uptake is at least in part due to a suppression of NIS specific transcription. Therefore, TGF beta(1) may act as an autocrine or paracrine local modu lator of thyroid hormone synthesis by influencing NLS mRNA levels in t he thyroid.