Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor.
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.
Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. rseetha285@gmail.com
Seethalakshmi
S
Iyer
Rebecca
R
Bahn
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D049970:Graves Ophthalmopathy / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000032:analysis*; D008024:Ligands; D058990:Molecular Targeted Therapy; D009915:Orbit / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018828:Immunoglobulins, Thyroid-Stimulating; D008024:Ligands; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin; D017526:Receptor, IGF Type 1