title: Iodide, cytokines and TSH-receptor expression in Graves' disease.
abstract: The present study was initiated to characterize thyrotropin receptor (TSH-R) expression in thyroids from patients with Graves' disease, as well as parameters that influence TSH-R expression either causally, such as interferon-gamma (IFN-gamma), the leading candidate among the cytokines thought to play a key role in the initiation of autoimmune thyroid disease, or therapeutically, such as iodide, which is used to prepare patients for surgery. Our data show that there is an average 4-fold increase of TSH-R mRNA levels in the thyroids of Graves' patients coming to surgery, which is paralleled by an increase in TSH-R protein levels and TSH binding capacity. The increase does not appear to be related to IFN-gamma since IFN-gamma transcripts are barely detectable in most Graves' patients. Iodide treatment causes a 2-fold decrease in TSH-R expression in association with significant decreases in major histocompatibility complex (MHC) class I and class II gene expression. These last data are compatible with a recently enunciated "transcription factor hypothesis" according to which abnormally high TSH-R and MHC class I and class II gene expression in Graves' thyroids are the result of a loss of the normal negative regulation of these genes necessary to allow the normal growth and function of the gland, yet preserve self-tolerance.
authors.affiliation: Department of Clinical Endocrinology, Hannover Medical School, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schuppert
authors.forename: W
authors.initials: W
authors.lastname: Hiller
authors.forename: G
authors.initials: G
authors.lastname: Weinland
authors.forename: C
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: A
authors.initials: A
authors.lastname: von zur Mühlen
authors.forename: L D
authors.initials: LD
authors.lastname: Kohn
mesh_terms: D015870:Gene Expression; D006111:Graves Disease / Q000188:drug therapy / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007454:Iodides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007454:Iodides; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D007371:Interferon-gamma