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

Agretti, Patrizia; Marco, Giuseppina De; Servi, Melissa De; Marcocci, Claudio; Vitti, Paolo; Pinchera, Aldo; Tonacchera, Massimo

doi:10.1530/eje.1.01900

Cited by 41 publications

(25 citation statements)

References 37 publications

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“…Notably, the TSH concentrations (0.1-2 mM) used in this study were higher than those found in the general population and in patients with hypothyroidism, although they were similar to the concentrations used for cultured nonthyrocytes, such as 3T3-L1 preadipocytes (Bell et al 2002), fibroblasts (Agretti et al 2005), aortic tissue, and umbilical cord endothelial cells (Balzan et al 2012). Coexisting growth factors/cytokines, such as insulin-like growth factor 1, may function synergistically to augment TSH signaling in vivo (Tian et al 2010), which may account for the lower TSH concentration in the human body.…”

Section: Discussionsupporting

confidence: 43%

Effects of TSH on the function of human umbilical vein endothelial cells

Tian¹,

Zhang²,

Liu³

et al. 2014

Journal of Molecular Endocrinology

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Recent studies have reported that subclinical hypothyroidism (SCH) is associated with atherosclerosis (AS). Thyroid hormone is maintained at normal levels in patients with SCH, whereas TSH is increased. However, the pathogenesis of AS in association with SCH is only partially understood. In addition, endothelial dysfunction plays an important role in the development of AS. The purpose of the present research was to study the direct effect of TSH on human umbilical vein endothelial cells (HUVECs). The expression of some genes associated with endothelial dysfunction after treatment with TSH was evaluated by real-time PCR and western blotting respectively. At first, we showed that the TSH receptor (TSHR) is expressed in HUVECs. We also provide evidence indicating that TSH treatment promotes tumor necrosis factor a-induced endothelial cells interactions by upregulating the expression of the adhesion molecules intercellular adhesion molecule-1. Furthermore, the expression of endothelial nitric oxide synthase (eNOS) and prostacyclin (PGI 2 ) was significantly attenuated following treatment with TSH in dose-and time-dependent manner. Conversely, the results indicated that TSH upregulated endothelin-1 (ET1) mRNA and protein expression in HUVECs, similar effects were observed for plasminogen activator inhibitor-1 (PAI1) after treatment with various concentrations of TSH. Taken together, these results demonstrate that elevated TSH can promote endothelial dysfunction by altering gene expression in HUVECs.

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Section: Discussionsupporting

confidence: 43%

Effects of TSH on the function of human umbilical vein endothelial cells

Tian¹,

Zhang²,

Liu³

et al. 2014

Journal of Molecular Endocrinology

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“…It should be noted that the TSH concentrations used in the present study were higher than that in normal people or patients with hypothyroidism, similar to the concentrations used for thyrocytes in culture 23 or for nonthyrocytes in culture, such as 3T3-L1 preadipocytes 24 and fibroblasts. 25 The reason for using a lower concentration of TSH in human body is possibly the synergistic action of coexisting growth factors/cytokines such as IGF-1 to augment TSH signaling in vivo. 23 The data presented strongly support the role of cAMP as a mediator of the stimulatory effects of TSH on HMGCR gene expression.…”

Section: Discussionmentioning

confidence: 99%

A Novel Role for Thyroid-Stimulating Hormone: Up-Regulation of Hepatic 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Expression Through the Cyclic Adenosine Monophosphate/Protein Kinase A/Cyclic Adenosine Monophosphate–Responsive Element Binding Protein Pathway

et al. 2010

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Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate-responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized rats, the production of endogenous thyroid hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010;52:1401-1409 H ypothyroidism is well known to be associated with elevated serum TC, which can result in hypercholesterolemia. 1,2 The underlying mechanism is widely thought to be TH deficiency.However, elevation of serum TC has also been observed in patients with subclinical hypothyroidism (SCH), in which TSH is elevated but TH stays within its normal range. 1,3,4 Thus, the development of

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“…Although it is widely accepted that TAO is an autoimmune disorder, its pathogenesis is unclear. Several studies have noted a strong correlation between antibodies to thyrotropin receptor and TAO in Graves' disease [1][2][3][4][5][6], and serum TRAb levels have been found to correlate…”

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confidence: 99%