Effects of Thyroid hormone on Cardiomyocytes and on Glioma differentiation and proliferation

Liappas, Alexandros (2012) Effects of Thyroid hormone on Cardiomyocytes and on Glioma differentiation and proliferation. Doctoral thesis, University of Central Lancashire.

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The action of thyroid hormone (TH) on cell growth, differentiation and survival during development may be of therapeutic relevance. The present study investigated the potential effects of long-term TH treatment on cardiomyocytes and on glioma tumour cell lines. This study employed neonatal cardiomyocytes, 1321N1 cell line, an astrocytoma grade II, and U87MG, a glioblastoma grade IV. Cells were exposed for 2 and 4 days in culture medium deprived of T3 (non-treated cells) and in a medium containing either 1 nM T3 (at near physiological range) or 500 nM T3 (supraphysiological). From the initial study on cardiomyocytes, the results show that phenylephryne (PE) can induce cell growth and this effect was mediated by T3. For the glioma cell lines the results show that T3 at 1 nM can promote cell re-differentiation in both cell lines. However, T3 had a preferential effect on suppressing cell proliferation only in the high grade glioma cell line. Thus, in 1321N1 cell line, T3 increased cell proliferation (2 days) which declined thereafter (4 days) without having any effect on cell survival. In U87MG cell line, T3 resulted in marked suppression of cell proliferation without increasing cell injury. At the molecular level, a 2.9 fold increase in the expression of TRα1 receptor was observed in U87MG cells as compared to 1321N1, p<0.05. TRβ1 receptor was undetectable in both cell lines. These changes corresponded to a distinct pattern of growth signalling activation induced by T3 treatment. The results also show that T3 had no significant effect on ERK activation in both cell lines, but significantly (p<0.05) increased phospho-Akt levels in 1321N1 cell line. At higher dose, T3 also induced cell differentiation in both cell lines and suppressed proliferation while increased cell injury in U87MG cells. It can be concluded from these results that T3 can re-differentiate glioma tumour cells. However, the effect of T3 on cell proliferation appears to be dependent on the type of tumour cell line with aggressive tumours to be more sensitive to thyroid hormone treatment. TRα1 receptor may, at least in part, be implicated in this response.

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