Posttranscriptional actions of triiodothyronine on Tshb expression in T alpha T1 cells: New insights into molecular mechanisms of negative feedback

Autor(es)

Bargi-Souza, Paula ^[1] ; Goulart-Silva, Francemilson ^[1] ; Nunes, Maria Tereza ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 478, p. 45-52, DEC 15 2018.
• Citações Web of Science: 1

Resumo

Rapid actions of triiodothyronine (T3) on thyrotropin (TSH) synthesis and secretion have been described in hypothyroid male rats. However, the molecular mechanisms remain unknown. T alpha T1 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 alpha V beta 3 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 alpha V beta 3 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-alpha V beta 3 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-alpha V beta 3 integrin interaction at the plasma membrane of thyrotrophs and add new insights to the molecular mechanisms involved in T3 negative feedback loop. (AU)

• Processo FAPESP: 13/05629-4 - Ações genômicas vs não genômicas dos hormônios tiroidianos: mudanças de paradigmas, implicações fisiológicas e perspectivas terapêuticas
• Beneficiário: Maria Tereza Nunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/17813-9 - Ações rápidas da triiodotironina (t3) sobre a expressão e secreção de tsh: novos mecanismos envolvidos no feedback negativo.
• Beneficiário: Paula Bargi de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/25888-7 - Caracterização das bases moleculares envolvendo a expressão dos genes do relógio circadiano da adenohipófise em diferentes estados tiroidianos e as consequências sobre a síntese/secreção dos hormônios hipofisários
• Beneficiário: Paula Bargi de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado