Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes

Davies, Terry F.; Teng, C.S.; McLachlan, Sandra M.; Smith, Bernard Rees; Hall, R.

doi:10.1016/0303-7207(78)90072-2

Cited by 72 publications

(20 citation statements)

References 23 publications

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“…TSH binding activity in fat tissue has long been reported (Gorman et al 1975, Mullin et al 1976, Davies et al 1978, Konishi et al 1982. Since the TSH receptor (TSHR) has been detected in both preadipocytes and adipocytes (Trokoudes et al 1979, Haraguchi et al 1996b, 1999, Crisp et al 1997, we hypothesize that it may play a role in adipose tissue differentiation.…”

Section: Introductionmentioning

confidence: 74%

TSH stimulates adipogenesis in mouse embryonic stem cells

Lü¹,

Lin²

2007

Journal of Endocrinology

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Although TSH is the main regulator of thyroid growth and function, TSH binding activity in fat has long been reported. Since the TSH receptor (TSHR) has been detected in both preadipocytes and adipocytes, we hypothesized that it may play a role in adipose differentiation. Here, we use an in vitro model of adipogenesis from mouse embryonic stem (ES) cells to define TSH function. Directed differentiation of ES cells into the adipose lineage can be achieved over a 3-week period. Although adipocyte differentiation is initiated early in the development of cultured ES cells, TSHR up-regulation is precisely correlated with terminal differentiation of those adipocytes. The adipocytes express TSHR on the cell surface and respond to TSH with increased intracellular cAMP production, suggesting the activation of the protein kinase A signaling pathway. To determine whether TSH impacts adipogenesis, we examined how adipocytes responded to TSH at various points during their differentiation from cultured ES cells. We found that TSH greatly increases adipogenesis when added in the presence of adipogenic factors. More importantly, our data suggest that TSH also stimulates adipogenesis in cultured ES cells even in the absence of adipogenic factors. This finding provides the first evidence of TSH being a pro-adipogenic factor that converts ES cells into adipocytes. It further highlights the potential of ES cells as a model system for use in the study of TSH's role in the regulation of physiologically relevant adipose tissue.

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Section: Introductionmentioning

confidence: 74%

TSH stimulates adipogenesis in mouse embryonic stem cells

Lü¹,

Lin²

2007

Journal of Endocrinology

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“…In addition, TSH binding sites were demonstrated by covalent crosslinking in homogenates of human eye muscle tissue (containing both extraocular muscle cells and perimysial connective tissue) (17). However, an earlier study failed to detect radiolabeled TSH binding to human retroorbital fat membranes (18). We have suggested the presence of functional TSH receptors on cultured retroocular fibroblasts in our demon¬ stration of enhanced expression of intercellular adhesion mole¬ cule-1 (19) and a 72-kDa heat shock protein (20) following treatment of cultures with IgGs derived from patients with Graves' ophthalmopathy having high thyroid-stimulating im¬ munoglobulin levels.…”

Section: Resultsmentioning

confidence: 97%

Detection of TSH Receptor RNA in Cultured Fibroblasts from Patients with Graves' Ophthalmopathy and Pretibial Dermopathy

Heufelder

Dutton

Sarkar

et al. 1993

Thyroid

164

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Fibroblasts are target cells for the autoimmune process in Graves' ophthalmopathy and pretibial dermopathy. Because the autoantigen involved in the hyperthyroidism of Graves' disease is the TSH receptor, we sought to determine whether RNA encoding this receptor might be present in retroocular and pretibial fibroblasts. RNA was reverse transcribed and the resulting cDNA was amplified by the polymerase chain reaction using primers spanning a region of the extracellular domain of the human TSH receptor. The predicted amplified product, verified by direct sequencing, was detected when RNA was derived from fibroblasts, but not from the nonfibroblast cells studied. The demonstration in fibroblasts of RNA encoding this important autoantigen in Graves' disease suggests that the TSH receptor might play a role in the pathogenesis of the connective tissue manifestations of this disease.

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“…The concept that adipose cells might express TSHr was formulated in 1964 by Rodbell (23) who demonstrated TSH stimulated lipolysis in rat epididymal cells showing for the first time extrathyroidal expression of the TSHr. Subsequent reports demonstrated specific TSH binding to guinea pig adipose and retro-ocular tissue (24) or to porcine orbital connective tissue membranes (25). In addition, guinea pig brown and white adipose tissues were shown to express TSHr mRNA (26).…”

Section: Discussionmentioning

confidence: 97%

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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Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes

Cited by 72 publications

References 23 publications

TSH stimulates adipogenesis in mouse embryonic stem cells

TSH stimulates adipogenesis in mouse embryonic stem cells

Detection of TSH Receptor RNA in Cultured Fibroblasts from Patients with Graves' Ophthalmopathy and Pretibial Dermopathy

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

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