Localization and Clinical Significance of Thyrotropin Receptor mRNA Expression in Orbital Fat and Eye Muscle Tissues from Patients with Thyroid-Associated Ophthalmopathy

Hiromatsu, Yuji; Sato, Masayuki; Inoue, Yoshio; Koga, Masahiro; Miyake, Ikuyo; Kameo, Junko; Tokisawa, Shiro; Yang, Damu; Nonaka, Kyohei

doi:10.1089/thy.1996.6.553

Cited by 37 publications

(21 citation statements)

References 33 publications

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“…The TSHr has been shown to be highly expressed in adipocytes in vivo (28). Numerous results from several laboratories now suggest that the TSHr is expressed in various human extrathyroidal tissues (29,30,31). The presence of the TSHr in human orbital tissue and orbital fibroblasts was demonstrated by using RT-PCR in 1993 (8,9), but the possibility of an illegitimate transcription was raised (32,33,34).…”

Section: Discussionmentioning

confidence: 99%

Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

et al. 2005

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Objective: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue in the human orbit. Design: The aim of this study was to investigate the thyrotropin receptor (TSHr) expression in orbital fibroblasts from TAO patients undergoing adipocytic differentiation. Methods: Retro-ocular tissue and skin were obtained from five patients undergoing orbital decompression surgery for TAO and placed in culture. Proliferating fibroblasts were subjected to adipocytic differentiation for 10 days. Total RNA was isolated from fibroblasts and was reverse transcribed. TSHr mRNA levels were determined by real-time PCR. cAMP was determined by radioimmunoassay (RIA) after fibroblast incubation with the substances to test. Results: Orbital differentiated fibroblasts became rounded and acquired lipid droplets. The amount of TSHr mRNA in these fibroblasts was higher than fibroblasts not subjected to adipocytic differentiation. Immunocytochemical analysis showed TSHr protein in differentiated orbital fibroblasts. Differentiated orbital fibroblasts stimulated with bovine (b) TSH showed a cAMP production greater than that in paired undifferentiated cultures. A specific thyroid-inhibiting antibody (TBAb) inhibited cAMP production after bTSH challenge, and a thyroid-stimulating antibody (TSAb) stimulated cAMP production in differentiated fibroblasts. Conclusions: We suggest that orbital fibroblasts subjected to adipocytic differentiation increase TSHr expression that responds specifically to bTSH and TSAb stimulation, and to TBAb inhibition. European Journal of Endocrinology 152 777-784

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Section: Discussionmentioning

confidence: 99%

Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

et al. 2005

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“…Because this receptor is considered a candidate antigen involved in the extrathyroidal manifestations of Graves' disease, its presence has been sought in human orbital and skin tis¬ sues (1). Both full-length TSHR mRNA and a 1.3-kb vari¬ ant TSHR transcript have been detected in normal and Graves' orbital connective tissues using reverse-transcriptase polymerase chain reaction (RT-PCR) (2)(3)(4)(5)(6)(7), and thy¬ rotropin (TSH)-like immunoreactivity has been reported in these tissues (8,9). In addition, two recent studies have demonstrated TSHR mRNA in normal thymus using Northern blotting or RT-PCR (10,11).…”

Section: Introductionmentioning

confidence: 99%

Thyrotropin Receptor Expression in Adrenal, Kidney, and Thymus

Dutton

Joba

Spitzweg

et al. 1997

Thyroid

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Because the thyrotropin receptor (TSHR) has long been considered a thyroid-specific protein, its presence in extrathyroidal tissues has been controversial. In this study, we sought to detect and quantify this potentially low abundance mRNA in various extrathyroidal tissues using liquid hybridization analysis (LHA) and to detect protein with immunohistochemical studies. Strongly positive protected bands, indicating the presence of both intact (2.4 kb) and variant (1.3 kb) TSHr mRNA, were apparent in LHA gel lanes corresponding to normal thyroid, Graves' thyroid, and thymus. Less abundant protected bands of the same sizes were present in lanes corresponding to normal adrenal, and samples from normal kidney were faintly positive. The full-length transcript:variant transcript ratio was approximately 1:1 in all positive tissues. Immunohistochemical analysis of TSHR-like reactivity in paraffin-embedded thymus, adrenal, and kidney revealed specific staining in each of these tissues. No TSHR mRNA or TSHR-like immunoreactivity was detected in samples from several other normal human tissues. We conclude that measurable TSHR mRNA and protein expression is not restricted to the thyroid gland. Further study is warranted to determine whether these extrathyroidal receptors play a role in normal physiology or in disease.

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“…These effects can induce thyroid autoimmunity, and recent data have suggested that both the immune-mediated and direct thyroid-toxic effects of IFN play a role in its etiology (38). Our previous study found that the expression of thyrotropin receptor (TSH-R) mRNA in orbital fat tissue from patients with Graves' ophthalmopathy significantly correlated with orbital fat volume and the severity of ophthalmopathy (40). These results suggest that the expression of TSH-R in the orbit may play a role in the pathogenesis and clinical manifestations of ophthalmopathy.…”

Section: Discussionmentioning

confidence: 99%

Graves' ophthalmopathy and tongue cancer complicated by peg-interferon α-2b and ribavirin therapy for chronic hepatitis C: A case report and review of the literature

Nagao

Hiromatsu²,

Nakashima³

et al. 2008

Mol Med Rep

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Abstract. Hepatitis C virus (HCV) infection induces not only chronic liver disease, but also extrahepatic manifestations such as thyroid disease and oral cancer. Thyroid dysfunction is also a complication known to be associated with interferon (IFN) therapy for HCV infection. We report on a 69-year-old Japanese man who developed Graves' ophthalmopathy and tongue cancer (malignant transformation of leukoplakia) while receiving peg-interferon (Peg-IFN) α-2b and ribavirin (RBV) treatment for chronic hepatitis C. This patient had no history of thyroid disease before the combination therapy, but did have bilateral leukoplakia of the tongue. The leukoplakia lesions did not change until 20 weeks after the start of the combination therapy, and ophthalmopathy was not diagnosed until 47 weeks later. As ophthalmopathy is considered to be a severe adverse event induced by Peg-IFN α-2b plus RBV, therapy was discontinued after 47 weeks. The patient received a partial glossectomy to remove the malignant neoplasm as well as extraocular muscle surgery for the ophthalmopathy, and was treated with an antithyroid agent and steroids. In conclusion, it is necessary to clinically examine organs other than the liver in patients with HCV infection.

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Localization and Clinical Significance of Thyrotropin Receptor mRNA Expression in Orbital Fat and Eye Muscle Tissues from Patients with Thyroid-Associated Ophthalmopathy

Cited by 37 publications

References 33 publications

Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

Thyrotropin Receptor Expression in Adrenal, Kidney, and Thymus

Graves' ophthalmopathy and tongue cancer complicated by peg-interferon α-2b and ribavirin therapy for chronic hepatitis C: A case report and review of the literature

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