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thyrotropin receptor

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https://www.readbyqxmd.com/read/28195550/novel-germline-mutation-leu512met-in-the-thyrotropin-receptor-gene-tshr-leading-to-sporadic-non-autoimmune-hyperthyroidism
#1
Stephanie A Roberts, Jennifer E Moon, Andrew Dauber, Jessica R Smith
BACKGROUND: Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in the TSHR gene who presented with accelerated growth, enlarging head circumference, tremor and thyrotoxicosis...
February 14, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28181228/thyrotropin-receptor-gene-expression-in-the-association-between-chronic-spontaneous-urticaria-and-hashimoto-s-thyroiditis
#2
Maria R C Silvares, Maria R P Fortes, Renata de A M L Nascimento, Carlos R Padovani, Hélio A Miot, Célia R Nogueira, Gláucia M F da S Mazeto
BACKGROUND: Chronic spontaneous urticaria (CSU) may be associated with autoimmune thyroid diseases, and the Autologous Serum Skin Test (ASST) is an autoreactivity marker. The thyrotropin (TSH) and TSH receptor (TSHR) could play a role in the pathogenesis of CSU. The aim of this study was to evaluate ASST positivity and TSHR gene expression in healthy skin and ASST wheals in euthyroid women with CSU, with (14 patients) and without (15 patients) Hashimoto's thyroiditis (HT). METHODS: ASST was performed and TSHR gene expression studied in wheals induced by ASST and in healthy skin...
February 8, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28173961/a-screen-for-modulators-reveals-that-orexin-a-rapidly-stimulates-thyrotropin-releasing-hormone-expression-and-release-in-hypothalamic-cell-culture
#3
Antonieta Cote-Vélez, Anabel Martínez Báez, Leticia Lezama, Rosa María Uribe, Patricia Joseph-Bravo, Jean-Louis Charli
In the paraventricular nucleus of the mammalian hypothalamus, hypophysiotropic thyrotropin releasing hormone (TRH) neurons integrate metabolic information and control the activity of the thyroid axis. Additional populations of TRH neurons reside in various hypothalamic areas, with poorly defined connections and functions, albeit there is evidence that some may be related to energy balance. To establish extracellular modulators of TRH hypothalamic neurons activity, we performed a screen of neurotransmitters effects in hypothalamic cultures...
February 2, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28134999/pathogenesis-of-hyperthyroidism
#4
Ishita Singh, Jerome M Hershman
Hyperthyroidism is a form of thyrotoxicosis in which there is excess thyroid hormone synthesis and secretion. Multiple etiologies can lead to a common clinical state of "thyrotoxicosis," which is a consequence of the high thyroid hormone levels and their action on different tissues of the body. The most common cause of thyrotoxicosis is Graves' disease, an autoimmune disorder in which stimulating thyrotropin receptor antibodies bind to thyroid stimulating hormone (TSH) receptors on thyroid cells and cause overproduction of thyroid hormones...
December 6, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/28127991/tshr-as-a-therapeutic-target-in-graves-disease
#5
Terry Smith
Introduction Graves' disease (GD) and thyroid-associated ophthalmopathy (TAO) are thought to result from actions of pathogenic antibodies mediated through the thyrotropin receptor (TSHR). This leads to the unregulated consequences of the antibody-mediated receptor activity in the thyroid and connective tissues of the orbit. Recent studies reveal antibodies that appear to be directed against the insulin-like growth factor-I receptor (IGF-IR). Areas covered In this brief article, I attempt to review the fundamental characteristics of the TSHR, its role in GD and TAO, and its relationship to IGF-IR...
January 27, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28123504/identification-and-functional-characterization-of-a-novel-thyrotropin-receptor-mutation-v87l-in-a-chinese-woman-with-subclinical-hypothyroidism
#6
Hong-Mei Zhang, Ya-Qin Zhou, Yan Dong, Qing Su
The thyrotropin receptor (TSHR) gene has been defined as a highly mutable gene. Mutations in the TSHR gene result in either gain or loss of the receptor function. Subclinical hypothyroidism (SH) is a clinical condition defined as an elevated serum TSH level associated with normal free thyroxine and free triiodothyronine. Chronic autoimmune thyroiditis is the most frequent cause of subclinical hypothyroidism in adults. In rare cases, a loss-of-function mutation of TSHR is the cause of SH. In the present study, a novel TSHR mutation (V87L; confirmed to be a loss-of-function mutation) was identified in a 59-year-old Chinese woman, as the potential cause of the patient's subclinical hypothyroidism...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28099999/high-level-intrathymic-thyrotrophin-receptor-expression-in-thyroiditis-prone-mice-protects-against-the-spontaneous-generation-of-pathogenic-thyrotrophin-receptor-autoantibodies
#7
S M McLachlan, H A Aliesky, B Banuelos, S Lesage, R Collin, B Rapoport
The thyrotrophin receptor (TSHR) A-subunit is the autoantigen targeted by pathogenic autoantibodies that cause Graves' hyperthyroidism, a common autoimmune disease in humans. Previously, we reported that pathogenic TSHR antibodies develop spontaneously in thyroiditis-susceptible non-obese diabetic (NOD).H2(h4) mice bearing a human TSHR A-subunit transgene, which is expressed at low levels in both the thyroid and thymus (Lo-expressor transgene). The present study tested recent evidence that high intrathymic TSHR expression protects against the development of pathogenic TSHR antibodies in humans...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28065941/di2-ethylhexyl-phthalate-disrupts-thyroid-hormone-homeostasis-through-activating-the-ras-akt-trhr-pathway-and-inducing-hepatic-enzymes
#8
Hanfeng Ye, Mei Ha, Min Yang, Ping Yue, Zhengyuan Xie, Changjiang Liu
Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063130/glucocorticoids-curtail-stimuli-induced-creb-phosphorylation-in-trh-neurons-through-interaction-of-the-glucocorticoid-receptor-with-the-catalytic-subunit-of-protein-kinase-a
#9
Israim Sotelo-Rivera, Antonieta Cote-Vélez, Rosa-María Uribe, Jean-Louis Charli, Patricia Joseph-Bravo
PURPOSE: Corticosterone prevents cold-induced stimulation of thyrotropin-releasing hormone (Trh) expression in rats, and the stimulatory effect of dibutyryl cyclic-adenosine monophosphate (dB-cAMP) on Trh transcription in hypothalamic cultures. We searched for the mechanism of this interference. METHODS: Immunohistochemical analyses of phosphorylated cAMP-response element binding protein (pCREB) were performed in the paraventricular nucleus (PVN) of Wistar rats, and in cell cultures of 17-day old rat hypothalami, or neuroblastoma SH-SY5Y cells...
January 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28061802/thyrotropin-producing-pituitary-adenoma-simultaneously-existing-with-graves-disease-a-case-report
#10
Nobuhiko Arai, Makoto Inaba, Takamasa Ichijyo, Hiroshi Kagami, Yutaka Mine
BACKGROUND: Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. CASE PRESENTATION: A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody...
January 6, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28054989/effects-of-long-term-in-vivo-exposure-to-di-2-ethylhexylphthalate-on-thyroid-hormones-and-the-tsh-tshr-signaling-pathways-in-wistar-rats
#11
Xinwen Dong, Jin Dong, Yue Zhao, Jipeng Guo, Zhanju Wang, Mingqi Liu, Yunbo Zhang, Xiaolin Na
Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA...
January 4, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28002738/construction-of-structural-mimetics-of-the-thyrotropin-receptor-intracellular-domain
#12
Olga Press, Tatiana Zvagelsky, Maria Vyazmensky, Gunnar Kleinau, Stanislav Engel
The signaling of a G protein-coupled receptor (GPCR) is dictated by the complementary responsiveness of interacting intracellular effectors such as G proteins. Many GPCRs are known to couple to more than one G protein subtype and induce a multitude of signaling pathways, although the in vivo relevance of particular pathways is mostly unrecognized. Dissecting GPCR signaling in terms of the pathways that are activated will boost our understanding of the molecular fundamentals of hormone action. The structural determinants governing the selectivity of GPCR/G protein coupling, however, remain obscure...
December 20, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27987211/inhibiting-thyrotropin-insulin-like-growth-factor-1-receptor-crosstalk-to-treat-graves-ophthalmopathy-studies-in-orbital-fibroblasts-in-vitro
#13
Robert F Place, Christine C Krieger, Susanne Neumann, Marvin C Gershengorn
BACKGROUND AND PURPOSE: Crosstalk between thyrotropin (TSH) receptors and insulin-like growth factor 1 (IGF-1) receptors initiated by activation of TSH receptors could be important in the development of Graves' ophthalmopathy (GO). Specifically, TSH receptor activation alone is sufficient to stimulate hyaluronic acid (HA) secretion, a major component of GO, through both IGF-1 receptor-dependent and -independent pathways. Although an anti-IGF-1 receptor antibody is in clinical trials, its effectiveness depends on the relative importance of IGF-1 versus TSH receptor signalling in GO pathogenesis...
February 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27986127/irisin-and-myostatin-levels-in-patients-with-graves-disease
#14
Mehmet Muhittin Yalcin, Mujde Akturk, Yusuf Tohma, Ethem Turgay Cerit, Alev Eroglu Altinova, Emre Arslan, Ilhan Yetkin, Fusun Balos Toruner
BACKGROUND AND AIMS: Skeletal muscle system, which is one of the primary targets for thyroid hormones, has an important role in energy metabolism. Some myokines such as irisin and myostatin have considerable effects on energy metabolism in addition to the musculoskeletal system. Our aim was to investigate circulating irisin and myostatin levels in patients with Graves' Disease (GD). METHODS: This study included 41 patients with GD who were in overt hyperthyroid status and 44 healthy subjects...
August 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/27927064/clinical-efficacy-of-yingliu-mixture-combined-with-metimazole-for-treating-diffuse-goitre-with-hyperthyroidism-and-its-impact-on-related-cytokines
#15
Hua Yang, Yilei Cong, Tengfei Wu, Hong Tang, Muhao Ma, Juanhua Zeng, Wenya Zhang, Zhen Lian, Xinyu Yang
CONTEXT: Yingliu mixture was developed in 1990s by Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine, for treating diffuse goitre with hyperthyroidism (Graves' disease, GD). Former studies have shown Yingliu mixture combined with methimazole (Y-M) can effectively improve thyroid function and decrease thyrotropin-receptor antibody level. Furthermore, we researched its impact on related cytokines to prove that Y-M improve patients' immunity status. OBJECTIVE: To observe the clinical efficacy of Y-M for treating GD...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#16
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27906859/recent-advances-in-nuclear-medicine-in-endocrine-oncology
#17
Markus Luster, Andreas Pfestroff, Frederik A Verburg
PURPOSE OF REVIEW: The purpose is to review recent advances concerning the role of nuclear medicine in endocrine oncology. RECENT FINDINGS: For I therapy of thyroid cancer a thyrotropin (TSH) more than 30 mU/l has for many years been deemed a condition sine qua non. However, new data show that patients with lower TSH levels at the time of ablation have the same rate of successful ablation as those with TSH more than 30 mU/l.I-124 combined integrated positron emission tomography and computed X-ray tomography was shown to be highly accurate in predicting findings on posttherapy radioiodine scanning and was shown to have a high prognostic power...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27864993/thyrotropin-alters-t-cell-development-in-the-thymus-in-subclinical-hypothyroidism-mouse-model
#18
K Wu, M Zhao, C Ma, H Zhang, X Liu, L Zhou, J Zhao, L Gao, D Wang
Subclinical hypothyroidism (SCH) is highly prevalent in the general population and is associated with potential deleterious effects. Although developing T cells express thyroid-stimulating hormone receptor (TSH-R), the changes of T cell development in thymus in SCH have not been fully clarified. SCH mouse model, which is characterized by elevated serum TSH but similar thyroid hormone levels, was used to study the role of TSH in T cell development. Thymus weight of SCH mice increased 18% compared with controls...
January 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27825413/risk-factors-of-lymphnode-metastasis-in-patients-with-thyroid-br-papillary-carcinoma-associated-with-graves-disease
#19
Yong Xie, Yue-Wu Liu, Meng-Yi Wang, Wen-Ze Wang, Hong-Feng Liu, Xiao-Yi Li, Wei-Sheng Gao
Objective To summarize the characteristics of lymph node metastasis in patients with papillary thyroid carcinoma accompanied with Graves disease,and to provide evidence for clinical treatment. Methods Totally 98 patients with papillary thyroid carcinoma and Graves disease who had been treated in Peking Union Medical College Hospital from January 2004 to December 2013 were divided into the lymph node metastasis positive group (n=34) and lymph node metastasis negative group (n=64). The general information,blood biochemical results,pathological results,and prognoses were compared between these two groups...
October 10, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/27821020/duox2-gene-mutation-manifesting-as-resistance-to-thyrotropin-phenotype
#20
Panudda Srichomkwun, Junta Takamatsu, Deborah A Nickerson, Michael J Bamshad, Jessica X Chong, Samuel Refetoff
Resistance to thyrotropin (TSH) (RTSH; defined by elevated TSH and a normal or hypoplastic thyroid gland) can be caused by mutations in genes encoding the TSH receptor and PAX8, and it has been linked to a locus on chromosome 15. In two nonconsanguineous families with nongoitrous euthyroid hyperthyrotropinemia, typical of the RTSH phenotype, exome analysis identified five rare DUOX2 gene variants (p.A649E, p.P1391A, p.R885L, p.G488R, and p.SF965-6SfsX29) found to be pathogenic. This form of nongoitrous dyshormonogenesis masquerades both clinically and biochemically as RTSH...
January 2017: Thyroid: Official Journal of the American Thyroid Association
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