Iodide, cytokines and TSH-receptor expression in Graves' disease.
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.
Schuppert
F
F
Department of Clinical Endocrinology, Hannover Medical School, Germany.
Hiller
W
W
Weinland
G
G
Hoang-Vu
C
C
von zur Mühlen
A
A
Kohn
L D
LD
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*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007454:Iodides; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D007371:Interferon-gamma