1997 Fiscal Year Final Research Report Summary
Gene Expression of Iodothyronine Deiodinase in Human
| Project/Area Number |
08671191
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kansai Medical University |
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Principal Investigator |
NISHIKAWA Mitsushige Kansai Medical University, 2nd Department of Internal Medicine, Associate Professor, 医学部, 助教授 (40156055)
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| Co-Investigator(Kenkyū-buntansha) |
TOYODA Nagaoki Kansai Medical University, 2nd Department of Internal Medicine, Assistant, 医学部, 助手 (90278630)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Deiodinase / Graves' disease / Mononuclear cells / mRNA / Gene expression |
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| Research Abstract |
Iodothyronine deiodinase catalyzes the conversion from thyroxine (T4) to triiodothyronine (T3), an active thyroid hormone. Two distinct deiodinases, Type 1 (D1) and Type 2 (D2) are known in both rodents and humans. D1 plays an important role to produce T3 and supply T3 to peripheral organs, whereas D2 is essential to the local supply of T3 in some specific organs including brain and pituitary.Complementary DNA for both D1 and D2 are identified and they were found to have a rare amino acid, selenocystein, at the catalytic unit. D1 in rats is increased by T3 and cyclic AMP,however, the regulatory mechanisms of D1 and D2 in humans are not clear partly because of the difficulty of the experimental materials. The purpose of the present study is to elucidate the mechanisms of the gene expression of D1 and D2 in human.
We utilized peripheral blood mononuclear cells (PBMC) for quantification of human D1. PBMC were isolated from normal volunteers and patients with hyperthyroidism using Ficoll-Hypaque gradient centrifugation from about 10 ml peripheral blood. D1 mRNA in PBMC was isolated and quantified by reverse transcriptase protein chain reaction using deleted mutated D1 cDNA.D1 mRNA of hyperthyroid Graves's disease was significantly higher than that of normal controls. There was a significant, positive correlation between D1 mRNA and serum T3 concentration. However, there was not a significant correlation between D1 mRNA in PBMC and serum activity of anti-thyrotropin receptor antibody. When T3 was added to cultured PBMC,D1 mRNA in PBMC was significantly increased. These findings indicate that the present method is valid for quantifying human D1 in PBMC and that D1 mRNA in PBMC is up-regulated by T3 in humans. We have shown an activity for D2 and D2 mRNA in human thyroid tissue. The regulatory mechanism of D1 and D2 in human thyroid tissue is being investigated.
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