Thyroid transcription factor-1 in orbital adipose tissues: potential role in orbital thyrotropin receptor expression

Abstract

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.

FIG. 1

Relative levels of thyroid transcription factor-1 (TTF-1) mRNA (normalized to 18S RNA) in orbital adipose tissue samples obtained from normal individuals (n = 11) and patients with Graves’ ophthalmopathy (GO; n = 18).

FIG. 2

Relative levels of thyroid transcription factor-2 (TTF-2) mRNA (normalized to 18S RNA) in orbital adipose tissue samples obtained from normal individuals (n = 10) and patients with Graves’ ophthalmopathy (GO; n = 16).

FIG. 3

Relative levels of thyrotropin receptor (TSHR) mRNA (normalized to 18S RNA) in orbital adipose tissue samples obtained from normal individuals (n = 19) and patients with Graves’ ophthalmopathy (GO; n = 28). *p < 0.05 between groups.

FIG. 4

Fold change (mean ± standard error of the mean [SEM]) in levels of thyroid transcription factor (TTF)-1, TTF-2, and thyrotropin receptor (TSHR) mRNA (normalized to 18S rRNA) in differentiated orbital preadipocyte cultures from patients with Graves’ ophthalmopathy (GO; n = 3). Results are expressed relative to parallel control (undifferentiated) orbital cultures from the same individuals. *p < 0.05 compared to control values.