INCREASE IN REF-1 MESSENGER-RNA AND PROTEIN BY THYROTROPIN IN RAT-THYROID FRTL-5 CELLS

Thyrotropin (TSH) induces the expression of fos and jun family genes i n thyroid cells. The DNA-binding activity of these gene products (AP-1 ) has been shown to be enhanced by ubiquitous nuclear redox factor-1 ( Ref-l), We thus examined whether TSH regulates Ref-1 gene expression i n rat thyroid FRTL-5 cells, Northern blot analysis revealed that the a bundance of Ref-1 mRNA significantly increased within 3 hours after TS H followed by a sustained increase until 12 hours, The increase was al so induced by treatment with forskolin but not in the presence of cycl oheximide, indicating that the TSH effect on Ref-l mRNA is mediated by intracellular cAMP and requires de novo protein synthesis. Consistent with the elevation of the mRNA level, Western blot analysis showed an increase in Ref-1 protein 3 hours after TSH. The level continued to i ncrease until 12 hours, These results suggested that increased Ref-l b y TSH might regulate the binding activity of AP-1 in thyroid cells, Co nsidering that Ref-l also has a DNA repair function, Ref-l may play du al roles in gene regulation and DNA repair processes in thyroid cells. (C) 1997 Academic Press.