Non genomic actions of triiodothyronine (T3) on the expression polyadenylation and distribution of TSH granules in thyrotrophs of hypothyroid rats / Ações não genômicas da triiodotironina (T3) sobre a expressão, poliadenilação e distribuição dos grânulos de TSH nos tireotrofos de ratos hipotireiodeos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

The thyroid-stimulating hormone (TSH) is the main regulator of the synthesis and secretion of thyroid hormones (TH), which exert a negative feedback mechanism in the pituitary by reducing the synthesis of β and α (CGA - Glycoprotein hormones alpha chain) chains through mechanisms that involve changes in the transcription of genes that encode these proteins (known as genomic action). However, in the last decade, an increasing body of evidence has shown that, in parallel with the classical genomic mechanisms, some TH actions might be elicited in a short period time (seconds to minutes), and in the presence of gene transcription inhibitors, which indicates that TH can also act nongenomically. In the present study we evaluate if TH could regulate some steps of the expression of β TSH and CGA in a short period of time, which might provide evidence that they could act by non genomic mechanisms. For this, the expression and polyadenylation of alpha (CGA) and β subunits of TSH mRNA, and TSH content, were evaluated by real time PCR and western blot, respectively, in thyroidectomized (hypothyroid) rats, 30 min after they were subjected or not to physiological or saturating doses of T3. It was observed that hyroidectomyzed animals treated with saline (Tx) presented an increase of 10 and 4 times in the content of βTSH and CGA mRNA, respectively, and in the βTSH / CGA ratio compared with control group. The saturating dose of T3 did not alter the βTSH and CGA mRNAs content, but the physiological dose reduced them at 52 and 34% respectively, without changing the βTSH / CGA ratio, compared with Tx group. The RACE-PAT assay showed that the Tx rats presented an increase in the mRNA βTSH poly-A tail length, whereas no change was observed to the mRNA of CGA. The acute and saturating dose of T3 caused a 17% reduction in the length of mRNA βTSH poly-A tail in hypothyroid animals compared with hypothyroid group. No changes were observed in the length of the poly-A tail of mRNA CGA, suggesting a specific effect of T3 on the β subunit polyadenylation. Through the Western blot/ECL, histochemistry and immunohistochemistry methods we could observe that T3 (in both doses used) promoted a 30% increase in TSH protein content, a decrease in βTSH labeling near thyrotrophs plasma membrane and increased the actin polymerization in the pituitary of hypothyroid animals, possibly by inhibiting the secretion of this hormone. Considering that these results were observed in 30 min, and some of them involve changes in post-transcriptional regulation of gene expression (polyadenylation), we can infer that in parallel to its genomic action, T3 acts by non genomic pathways in the regulation of the TSH synthesis and secretion.

ASSUNTO(S)

thyrotropin (tsh) tireotrofo non genomic actions poliadenilação secretion ações não genômicas polyadenylation thyroid hormone tirotrofina (tsh) hormônio tireoidiano thyrotroph secreção

ACESSO AO ARTIGO

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