Molecular Mechanisms of Expression of TSHR and Graves' Ophthaolmopathy

点击翻译按钮获取中文摘要

We have shown that functional TSHR has been expressed in rat adipose tissue and 3T3-L1 cells upon differentiation. Since the amount of expressed TSHR approaches to that of thyroid and also enlargement of fat tissue has been reported in Graves' ophthalmopathy, we believe that the exploration of mechanisms of TSHR expression is important for the understanding of pathogenesis of Graves' ophthalmopathy. Using rat preadipocyte and 3T3-L1 cultured cells, we obtained the findings below.1 ) Dedifferentiation of adipocyte by cytokines such as TGFィイD2βィエD2, TNFィイD2αィエD2 and IFNィイD2γィエD2 was accomopanied by the decreased expression of TSHR.2)Stimulation of differentiation of adipocytes by PPARィイD2γィエD2 activators was accompanied by the increased expression of TSHR whose responsiveness to TSH was well conserved.3)Transfection of preadipocytes with PPARg expressing adenovirus enhanced the PPARg activators on its actionon TSHR expression.4)Deoxyribonuclease 21 protection showed that nuclear extracts from differentiated 3T3-L1 cells strongly protected two sequences from -146 to -127 and -112 to -106 containing Ets-binding sites.5)We found two new nuclear proteins which binds to putative Ets binding site of TSHR, one decreased upon differentiation whereas the other increased.Using southwestern analysis, we are now trying to identify and get clonnes of the new nuclear proteins.