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 dei odinase (D1) gene expression, we measured the D1 mRNA levels in periph eral blood mononuclear cells (PBMC) in normal control subjects and in patients with Graves' disease. We used competitive reverse transcripta se-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. The D1 mRNA levels in PBMC were in creased significantly in patients with Graves' disease compared with t hat in normal controls. There was a significant (p < 0.01) positive co rrelation (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-depen dent manner. These findings indicate that PBMC D1 mRNA is actually up- regulated by T3 in vivo and we postulate that a vicious spiral of incr easing T3 and D1 is responsible for the exacerbation of thyrotoxicosis in hyperthyroid Graves' disease. (C) 1998 Academic Press.