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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., (Copyright © 2018. Published by Elsevier B.V.)

TSH, FSH and LH share the same glycoprotein alpha chain (CGA) as part of their protein structure. Therefore, it is possible that thyroid and gonadal dysfunction may affect the CGA expression. This study evaluated several steps of CGA synthesis and secretion in thyrotrophs and gonadotrophs of control and hypothyroid rats, acutely or chronically-treated with T3. Hypothyroidism increased the Cga mRNA expression and its association to ribosome, but decreased intracellular CGA content. These parameters were reversed after acute or chronic T3 treatment. We conclude that T3 not only down-regulates Cga mRNA expression, as expected, but also inhibits the association of Cga mRNA to ribosome, as well as the CGA secretion. These findings add novel insights into our understanding of the role of T3 on the regulation of the Cga gene expression and CGA secretion, which might have a potential repercussion in all pituitary glycoprotein hormone synthesis and secretion., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Iodide excess acutely downregulates NIS mRNA expression, as already demonstrated. PCCl3 cells treated or not with NaI, NaI+NaClO(4) or NaI+Methimazole, for 30 min to 24 h, were used to further explore how iodide reduces NIS gene expression. NIS mRNA expression was evaluated by Real-Time PCR; its poly(A) tail length, by RACE-PAT; its translation rate, by polysome profile; total NIS content, by Western blotting. NIS mRNA decay rate was evaluated in actinomycin-D-treated cells, incubated with or without NaI for 0-6 h. Iodide treatment caused a reduction in NIS mRNA expression, half-life, poly(A) tail length, recruitment to ribosomes, as well as NIS protein expression. Perchlorate, but not methimazole, prevented these effects. Therefore, reduced poly(A) tail length of NIS mRNA seems to be related to its decreased half-life, in addition to its translation impairment. These data provide new insights about the molecular mechanisms involved in the rapid and posttranscriptional inhibitory effect of iodide on NIS expression., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Whereas it is well known that T3 inhibits TSHβ gene transcription, its effects on TSHβ mRNA stability and translation have been poorly investigated. This study examined these possibilities, by evaluating the TSHβ transcripts poly(A) tail length, translational rate and binding to cytoskeleton, in pituitaries of thyroidectomized and sham-operated rats treated with T3 or saline, and killed 30 min thereafter. The hypothyroidism induced an increase of TSHβ transcript poly(A) tail, as well as of its content in ribosomes and attachment to cytoskeleton. The hypothyroid rats acutely treated with T3 exhibited a reduction of TSHβ mRNA poly(A) tail length and recruitment to ribosomes, indicating that this treatment decreased the stability and translation rate of TSHβ mRNA. Nevertheless, acute T3 administration to sham-operated rats provoked an increase of TSHβ transcripts binding to ribosomes. These data add new insight to an important role of T3 in rapidly regulating TSH gene expression at posttranscriptional level., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)