Posttranscriptional actions of triiodothyronine on Tshb expression in TαT1 cells: New insights into molecular mechanisms of negative feedback

Rapid actions of triiodothyronine (T3) on thyrotropin (TSH) synthesis and secretion have been described in hypothyroid male rats. However, the molecular mechanisms remain unknown. TαT1 cells, a thyrotroph cell line, was used herein to characterize the possible non-genomic actions of T3 on the expression of alpha (Cga) and Tshb genes, and the posttranscriptional processing and translation of both transcripts. The involvement of αVβ3 integrin was also assessed. T3 quickly reduced Tshb mRNA content, poly(A) tail length and its association with ribosomes. The effect of T3 on Tshb gene expression was detected even in the presence of a transcription inhibitor. The decrease in Tshb mRNA content and polyadenylation depend on T3 interaction with αVβ3 integrin, while T3 reduced Cga mRNA content by transcriptional action. The translational rate of both transcripts was reduced by a mechanism, which does not depend on T3-αVβ3 integrin interaction. Results indicate that, in parallel with the inhibitory transcriptional action in Cga and Tshb gene expression, T3 rapidly triggers additional posttranscriptional mechanisms, reducing the TSH synthesis. These non-genomic actions partially depend on T3-αVβ3 integrin interaction at the plasma membrane of thyrotrophs and add new insights to the molecular mechanisms involved in T3 negative feedback loop.