Priority Programme: THYROID TRANS ACT
Translation of Thyroid Hormone Actions beyond Classical Concepts

PD Dr. Lars Moeller

Nonclassical thyroid hormone signaling mediated by thyroid hormone receptor beta

Thyroid hormones (TH) are essential for normal development, growth, and metabolism. They act as ligands of the thyroid hormone receptors (TRs) α and β. After hormone binding, the TRs attach to the DNA to induce gene expression, which is seen as their classical mode of action. Recently, it was discovered that TRs can also act independent of DNA binding: they can activate a cellular signaling pathway, the PI3K pathway, which then also induces gene expression, but mainly mediates antiapoptotic and prosurvival effects. This is characterized as nonclassical TH action. The challenge is now to dissect which effects of TH are mediated through which of the two mechanisms of the TRs, DNA-dependent or DNA-independent. To answer that question, we are using a mouse model, in which the TRβ was modified so that it does not bind to DNA anymore. All effects of TH mediated by this receptor are DNA-independent, which allows us to study purely nonclassical, DNA-independent effects of TH in a live animal model. For example, TH treatment of mice after myocardial infarction results in reduced infarct size and preserved ventricular function and after partial hepatectomy TH treatment inhibits apoptosis and stimulates hepatocyte proliferation. We suspect these beneficial effects to be consequences of prosurvival and antiapoptotic nonclassical TH action.

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Project Coordinator(s):

PD Dr. Lars Moeller
Universität Duisburg-Essen
Klinik für Endokrinologie und Stoffwechselerkrankungen
Hufelandstr. 55
45147 Essen
Phone: +49 201 723 6401
Fax: +49 201 723 5972
lars.moeller@uni-due.de