Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 P332

ECE2007 Poster Presentations (1) (659 abstracts)

Gq/11-dependent signaling of the tyhrotropin receptor regulates metallothionein 1 expression in human thyroid carcinoma cells

Thomas Buech 1 , Christer Baeck 1 , Nicola Nowak 2 & Thomas Gudermann 1

1Department of Pharmacology, Philipps University, Marburg, Germany; 2CRBA Gynecology & Andrology, Schering AG, Berlin, Germany.

Metallothioneins (MT) are cystein-rich intracellular proteins which exert anti-apoptotic effects by protecting cells against oxidative stress and DNA damage. Previously, expression of MT in normal and neoplastic thyroid tissue has been demonstrated. However, the thyroidal regulation of MT expression is widely unsettled. Thus, we investigated the expression of MT isoform 1 in human thyroid carcinoma cells (FTC-133-TSHR) upon stimulation with thyrotropin (TSH). Using quantitative RT-PCR we found that TSH led to a dose-dependent increase in MT-1 mRNA levels in these cells. To further characterize the signaling pathway involved in MT-1 induction we investigated thyroid carcinoma cells expressing a mutated TSH receptor incapable to couple to Gq/11 proteins (FTC-133 Y601H cells). In these cells, TSH still led to a marked increase in intracellular cAMP levels wheras an increase in inostiol phosphates was completely absent. Interestingly, TSH did not induce MT-1 in these cells, giving evidence that regulation of MT-1 was cAMP-independent but dependent on Gq/11-coupling. This finding was further corrobated by the fact that TSH-promoted incuction of MT-1 in FTC-133-TSHR cells was blocked by inhibitors of phospholipase C, whereas treatment with phorbol esters mimicked the effect of TSH. Finally, we investigated changes in MT-1 protein levels. Immunoblots and immunocytochemistry with MT-1 specific antibodies revealed a TSH-induced up-regulation of MT-1 in FTC-133-TSHR cells whereas no effect of TSH occurred in FTC-133 Y601H cells. The finding of Gq/11-dependent regulation of MT-1 by TSH adds further complexity to possible cAMP-independent functions of the TSH receptor.

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