Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease.
Transcription factors TTF-1 and Pax-8 control the expression of thyroid-specific genes crucial for thyroid function. It has been postulated that they may play a role in thyrotropin (TSH)-mediated augmentation of gene expression observed in some thyroid diseases including Grave's hyperthyroidism. Recently, we and others described the expression of two genes participating in thyroid hormone metabolism type I and type II deiodinase (D1 and D2, respectively) that are upregulated by TSH, although the mechanisms responsible for this effect are likely to be different. The aim of this study was to investigate whether there is a correlation between TTF-1 and Pax-8 mRNA levels and type I or type II 5' deiodinases expression in Graves' disease. D1 activity and mRNA level, as well as D2 activity and mRNA level, were significantly increased in Graves' disease in comparison to control tissues. D1, but not D2, activity correlated with its mRNA level in Graves' disease and toxic multinodular goitre. The TTF-1 mRNA level was not different between Graves' disease and control thyroids and no correlation between TTF-1 mRNA level and either D1 or D2 mRNA levels were found. The Pax-8 mRNA level was significantly increased in Graves' disease in comparison to control tissues and correlated with D2, but not D1, mRNA levels among all investigated groups of tissues. Our data suggest that transcription factor Pax-8 could be involved in the upregulation of D2 expression in the thyroid of Graves' patients.
Ambroziak
Michał
M
Department of Biochemistry, Medical Centre of Postgraduate Education, Warsaw, Poland. ambroz@amwaw.edu.pl
Pachucki
Janusz
J
Chojnowski
Krzysztof
K
Wiechno
Wiesław
W
Nauman
Janusz
J
Nauman
Alicja
A
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006044:Goiter, Nodular / Q000378:metabolism; D006111:Graves Disease / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D007453:Iodide Peroxidase / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D013961:Thyroid Gland / Q000201:enzymology / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D007202:Indicators and Reagents; D007527:Isoenzymes; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D000242:Cyclic AMP; D007453:Iodide Peroxidase; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C