Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease.
To evaluate the regulatory mechanism of human Type 1 iodothyronine deiodinase (D1) gene expression, we measured the D1 mRNA levels in peripheral blood mononuclear cells (PBMC) in normal control subjects and in patients with Graves' disease. We used competitive reverse transcriptase-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. The D1 mRNA levels in PBMC were increased significantly in patients with Graves' disease compared with that in normal controls. There was a significant (p < 0.01) positive correlation (r=0.698) between D1 mRNA level and serum T3 concentration. When PBMC from the normal volunteers were cultured with various doses of T3, the quantity of D1 mRNA increased significantly in a dose-dependent manner. These findings indicate that PBMC D1 mRNA is actually up-regulated by T3 in vivo, and we postulate that a vicious spiral of increasing T3 and D1 is responsible for the exacerbation of thyrotoxicosis in hyperthyroid Graves' disease.
Second Department of Internal Medicine, Kansai Medical University, Osaka, Moriguchi, 570, Japan.
M
M
Nishikawa
N
N
Toyoda
T
T
Yonemoto
Y
Y
Ogawa
S
S
Tabata
N
N
Sakaguchi
T
T
Tokoro
A
A
Gondou
M
M
Yoshimura
N
N
Yoshikawa
M
M
Inada
D005786:Gene Expression Regulation; D006111:Graves Disease / Q000097:blood* / Q000235:genetics; D006801:Humans; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014284:Triiodothyronine / Q000378:metabolism
D012333:RNA, Messenger; D014284:Triiodothyronine; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase