Graves' ophthalmopathy is an inflammatory autoimmune disorder of the orbit. The close clinical and temporal relationships between Graves' hyperthyroidism and ophthalmopathy have long suggested that both conditions derive from a single systemic process and share the thyrotropin receptor as a common autoantigen. This receptor is expressed not only in thyroid follicular cells, but also in orbital fibroblasts with higher levels measured in orbital cells from ophthalmopathy patients than in cells from normal individuals. Recent studies from several laboratories have shown that thyrotropin receptor activation in orbital fibroblasts enhances hyaluronic acid synthesis and adipogenesis, both cellular functions that appear to be upregulated in the diseased orbit. The phosphoinositide 3-kinase/Akt signaling cascade, along with other effector pathways including adenylyl cyclase/cAMP, appears to mediate these processes. Future therapies for this condition may involve inhibition of thyrotropin receptor signaling in orbital fibroblasts.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361679 | PMC |
| http://dx.doi.org/10.1016/j.beem.2011.10.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Linsitinib inhibits proliferation and induces apoptosis of both IGF-1R and TSH-R expressing cells.
Front Immunol
December 2024
Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.
Background: The insulin-like growth factor 1 receptor (IGF-1R) and the thyrotropin receptor (TSH-R) are expressed on orbital cells and thyrocytes. These receptors are targeted in autoimmune-induced thyroid eye disease (TED). Effective therapeutic treatment of TED inhibits activation of the IGF-1R/TSH-R complex.
View Article and Find Full Text PDFLinsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human Thyrocytes and in Mice.
Thyroid
December 2024
Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA.
Thyrotropin receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) have been shown to crosstalk in primary cultures of human thyrocytes (hThyros) and Graves' orbital fibroblasts. The phenomenon of TSHR/IGF-1R crosstalk has been largely studied in the pathogenesis of thyroid eye disease (TED) in human orbital fibroblasts. Here, we investigated the effects of inhibiting the IGF-1R-mediated contribution to crosstalk by linsitinib (Lins), a small-molecule IGF-1R kinase inhibitor, on TSH-induced regulation of thyroperoxidase (TPO) and thyroglobulin (TG) mRNAs and proteins in hThyros and on TPO and TG mRNAs and free thyroxine (fT4) levels in mice.
View Article and Find Full Text PDFSignificance of Thyroid Stimulating Immunoglobulin and Thyrotropin Receptor Antibody in Graves' Disease.
J Clin Endocrinol Metab
December 2024
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Context: Thyroid stimulating immunoglobulin (TSI) and thyrotropin receptor antibody (TRAb) are specific biomarkers for Graves' disease (GD), but their clinical characteristics are not fully understood.
Objectives: To clarify the clinical features and prognostic significance of TSI and TRAb in patients with GD.
Design: A retrospective data analysis and a follow-up study.
Best practices in the laboratory diagnosis, prognostication, prediction, and monitoring of Graves' disease: role of TRAbs.
BMC Endocr Disord
December 2024
Department of Endocrinology, Osmania Medical College & Osmania General Hospital, Hyderabad, Telangana, India.
Article Synopsis
- Graves' disease (GD) is an autoimmune disorder where the body's antibodies stimulate the TSH receptor, causing excessive thyroid hormone production.
- Diagnosis typically involves assessing symptoms and a thyroid panel, with specific tests for TSH Receptor Antibodies (TRAbs) aiding in diagnosis and management strategies.
- Recent guidelines from experienced endocrinologists emphasize the importance of TRAbs in GD management to improve effectiveness and decision-making for healthcare providers, particularly in South Asia.
2'-O-Galloylhyperin Prevents Tissue Remodeling in Thyroid Eye Disease: Prospects as a Thyrotropin Receptor Antagonist.
J Clin Endocrinol Metab
December 2024
Department of Endocrinology and Diabetes Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Context: Thyroid eye disease (TED) is a challenging condition owing to relentless orbital tissue remodeling, with thyrotropin receptor (TSHR) in orbital fibroblasts (OFs) serving as a promising therapeutic target.
Objective: This study seeks to discover potential TSHR inhibitors among US Food and Drug Administration (FDA)-approved drugs and evaluate their effects on TED-OFs.
Methods: Adipose tissues were sourced from the patients with or without TED.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!