Aim: 

Non genomic effects of Thyroid Hormones do not require interaction with nuclear receptors but can be mediated by aVb3 integrin and by cytoplasmic isoform of TRb1 which can associate with PI3K regulatory subunit. These effects are mimiked by the cell membrane impermeable T3 and T4-agarose. In chick embryo hepatocytes the mitogenic effect of T3 is dependent on short-term activation of PKC and MAPK but it is not mediated by integrin. In this work we analyze if in cultured chick embryo hepatocytes ,T3 proliferative effect uses a signalling pathway mediated by PI3K, NADPoxidase (NOX) and ROS production.

Methods: 

We have assayed: 1) the Wortmannin (W) and Ly294002 (Ly)effect on T3 stimulation of methyl thymidine incorporation in DNA 2) the Difenileiodonio (DPI) and Pefabloc (NOX inhibitors) effect on T3 stimulation of DNA synthesis 3) the production of ROS (using fluorescent probe Diclorofluorescein ) after T3 treatment and the effect of W , Ly, DPI and Pefabloc on ROS production 4) the activation of PI3K/Akt pathway by T3.

Results: 

Our data show that in these cells T3 induces a moderate increase of ROS production and that DPI and W block the increase of DNA synthesis and of ROS production provoked by T3 treatment.Preliminary experiments indicate that T3 increases PI3K/Akt activities.

Conclusion: 

These results suggest a new pathway for T3 mitogenic effect which involves NOX activation by PI3K/Akt and production of ROS that are known modulators of PKC and MAPK.