Adipogenesis in thyroid eye disease

Abstract

Purpose: Adipogenesis contributes to the pathogenesis of thyroid eye disease (TED). Thyrotropin receptor (TSHR) transcripts are present in orbital fat. This study was conducted to determine whether they are expressed as functional protein, and if so, whether this is restricted to TED orbits or to a particular stage in adipocyte differentiation.

Methods: Samples of fat were obtained from 18 TED-affected orbits and 4 normal orbits, and 9 were obtained from nonorbital locations. Frozen sections were examined by immunocytochemistry using monoclonal antibodies specific for the human TSHR. Samples were disaggregated and the preadipocytes separated from the mature by differential centrifugation and cultured in serum-free or DM and examined for morphologic changes, oil red O and TSHR staining, and TSH-induced cyclic adenosine monophosphate (cAMP) production.

Results: Marked immunoreactivity was observed in frozen sections from all three TED samples and faint staining in both normal orbital fat samples. In vitro, 1% to 5% of preadipocytes displayed TSHR immunoreactivity in five of six TED and two of three normal orbital samples and in three of five nonorbital samples. Differentiation, was induced in all 14 orbital samples. Three of four nonorbital samples contained occasional differentiated cells. Fifty percent to 70% of differentiating cells demonstrated receptor immunoreactivity. Two of three TED and four of four nonorbital preadipocytes in DM and/or mature adipocytes displayed a TSH-mediated increase in cAMP.

Conclusions: The results indicate that orbital fat TSHR transcripts are expressed as protein, which can be functional. This is not aberrant in TED orbits, although expression may be upregulated. The majority of preadipocytes undergoing differentiation express the receptor, indicating a key role for this population in one mechanism for increasing orbital volume.