Thyroid transcription factor-1 in orbital adipose tissues: potential role in orbital thyrotropin receptor expression.
Thyroid transcription factor-1 (TTF-1) is required for maximal expression of thyrotropin receptor (TSHR) in the thyroid. Extrathyroidal TSHR expression is detectable in normal orbital adipose tissues, with increased levels found in orbital tissues from patients with Graves' ophthalmopathy (GO), and in orbital preadipocyte cultures following differentiation. In order to determine whether TTF-1 might be involved in orbital TSHR expression, we used quantitative real-time polymerase chain reaction (PCR) to assess relative expression of this and other thyroid-associated transcription factors (TTF-2 and Pax-8) in GO orbital tissue specimens (n = 28) and cultures (n = 3), and in normal orbital tissues (n = 19) and cultures (n = 3). We detected TTF-1 and TTF-2 mRNA in GO and normal orbital tissue samples, with no difference in levels noted between the tissues. In the GO orbital cultures, TTF-1 mRNA was higher in differentiated than in control (undifferentiated) cultures (p < 0.05), while TTF-2 was unchanged. In the normal cultures, neither TTF-1 nor TTF-2 mRNA levels increased in differentiated cultures. Pax8 was undetectable in all orbital tissues and cell cultures. The presence of mRNA encoding TTF-1 in orbital tissues and cultures suggest that this transcription factor may play an important role in extrathyroidal, as it does in thyroidal, TSHR expression.
Bhattacharyya
Kalyan K
KK
Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota 55905, USA.
Coenen
Michael J
MJ
Bahn
Rebecca S
RS
D000251:Adenosine Triphosphatases; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers / Q000494:pharmacology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D009915:Orbit / Q000378:metabolism*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C477874:TTF2 protein, human