Expression levels of the thyrotropin receptor gene in autoimmune thyroid disease: coregulation with parameters of thyroid function and inverse relation to major histocompatibility complex classes I and II.
Using a human TSH receptor (TSH-R) cDNA probe, we investigated TSH-R transcript levels in 13 human thyroid fragments by Northern blot analysis; 7 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter, and 1 healthy thyroid gland were studied. TSH-R expression levels were variable, but displayed a close correlation to the expression of thyroid peroxidase (r = 0.703; P < 0.05), thyroglobulin (r = 0.817; P < 0.01), and the nuclear oncogene c-fos (r = 0.935; P < 0.001), but not c-myc. Overall, TSH-R transcript levels were low or absent in those thyroids in which expression of the major histocompatibility complex class I or II (MHC I or II) was high, thus establishing an inverse relation (MHC I, r = -0.791; P < 0.01; MHC II, r = -0.784; P < 0.01). In situ hybridization showed that apart from lymphocytes, thyroid cells themselves were the source of MHC II transcripts. gamma-Interferon expression was only detectable in 1 Hashimoto's goiter. Our findings suggest that next to lymphocyte infiltration, active regulatory events in the thyrocyte are responsible for the inverse relation between functional parameters (TSH-R, thyroid peroxidase, thyroglobulin, and c-fos) and immunological markers (MHC I and II).
Department of Clinical Endocrinology, Medizinische Hochschule Hannover, Germany.
F
F
Schuppert
M
M
Reiser
G F
GF
Scheumann
N E
NE
Heldin
P
P
Pring-Akerblom
S
S
Ede
G
G
Haverkamp
H
H
Dralle
A
A
Von zur Mühlen
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D017403:In Situ Hybridization; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013959:Thyroid Diseases / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D013961:Thyroid Gland / Q000503:physiopathology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D015335:Molecular Probes; D016760:Proto-Oncogene Proteins c-fos; D011989:Receptors, Thyrotropin