1994 Fiscal Year Annual Research Report

TSH受容体異常症の研究

Research Project

Project/Area Number	05670870
Research Institution	Nagasaki University
Principal Investigator	横山直方長崎大学, 医学部, 助手 (10240219)
Keywords	TSH受容体異常症 / 先天性原発性甲状腺機能低下症 / TSH不応症 / TSH受容体遺伝子
Research Abstract	常染色体劣性遺伝形式をとる先天性原発性甲状腺機能低下症で、1)正常部位に甲状腺はあるが腫大はない、2)血中TSHの生物学的活性は正常かまたはTSH連続負荷に反応しない、3)甲状腺自己抗体は陰性、の条件を満たす家系をTSH不応症と判定して、TSH受容体遺伝子の変異の有無を検討した。TSHの生物活性は患者血清からTSHを抽出し、ラットFRTL-5細胞のcAMP産生量で判定、さらにTSH連続負荷試験は3〜5日連続TSH負荷前後の^<131>I uptakeと甲状腺ホルモン値で判定した。患者末梢血リンパ球よりRNAを分離しRT-PCRを行い、TSH受容体cDNA断片を増幅後、直接シークエンス法によりその全塩基配列を決定した。対象の4家系のうち、1家系でTSH連続負荷試験の基準を完全には満たさなかったため、最終的には残りの3家系について遺伝子解析を行ない、TSH受容体異常の有無を検討した。RT-PCRで得たTSH-RcDNA断片の大きさはアガロールゲル上すべて対照と等しく、大きな欠失や挿入、スプライシングの異常は認めなかった。さらに、直接シークエンス法による解析では3症例ともシグナルペプチドを含むTSH受容体遺伝子に変異は認めなかった(Thyroid,4,255-259,1994)。TSH不応症は現在までこの症例を含め8家系が報告されているにすぎない。TSH不応症におけるTSH受容体異常はおそらく稀であり、この3家系についてはTSH受容体遺伝子に異常はなく、プロモーター領域やポストレセプターの異常などが疑われた。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Akira Takeshita: "Sequence analysis of the thyrotropin(TSH)receptor gene in congenital primary hypothyroidism associated with TSH unresponsiveness" Thyroid. 4. 255-259 (1994)
[Publications] Yuji Nagayama: "Studies on homologous desensitization of the thyrotropin receptor in 293 human embryonal kidney cells" Endocrinology. 135. 1060-1065 (1994)
[Publications] Yuji Nagayama: "High affinity binding of thyrotropin(TSH)and Thyroid-stimulating auto antibody for the TSH receptor extra cellular domain" Thyroid. 4. 155-159 (1994)
[Publications] Yuji Nagayama: "Exacerbation of thyroid autoimmunity by interferon α treatment in patients with chronic viral hepatitis: our studies and review of the literature" Endocrine Journal. 41. 565-572 (1994)
[Publications] Wentian Luo: "Immunohistochemical analysis of expression of nm23-H1/nucleoside diphosphate kinase in human thyroid careinomas: lack of correlation between its expression and lymph node metastasis" Thyroid. 3. 105-109 (1993)
[Publications] Wentian Luo: "Taql polymorphism in the human thyrotropin receptor gene(TSHR)" Hum Mol Genet. 2. 826- (1993)
[Publications] Hiroyuki Namba: "Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes" J Endocrinol Invest. 16. 87-93 (1993)
[Publications] Yuji Nagayama: "In vivo effect of gold compounds on thyroxine to triiodothyronine conversion by typeI5´-deiodinase in patients with rheumatoid arthritis" Horm Metab Res. 25. 657-658 (1993)
[Publications] Hiroyuki Namba: "Evidence of thyroid volume increase in normal subjects receiving excess iodide" J Clin Endocrinol Metab. 76. 605-608 (1993)
[Publications] Kazuya Eishima: "The significance of^<131>I treatment of metastatic thyroid carcinoma" Int J Oncol. 2. 877-882 (1993)
[Publications] Masako Tsuruta: "Long-term follow-up studies on iodine-131 treatment of hyperthyroid Graves´disease based on the measurement of thyroid volume by ultrasonography" Ann Nucl Med. 7. 193-197 (1993)

1994 Fiscal Year Annual Research Report

TSH受容体異常症の研究

Principal Investigator

横山 直方 長崎大学, 医学部, 助手 (10240219)

Research Products

[Publications] Akira Takeshita: "Sequence analysis of the thyrotropin(TSH)receptor gene in congenital primary hypothyroidism associated with TSH unresponsiveness" Thyroid. 4. 255-259 (1994)

[Publications] Yuji Nagayama: "Studies on homologous desensitization of the thyrotropin receptor in 293 human embryonal kidney cells" Endocrinology. 135. 1060-1065 (1994)

[Publications] Yuji Nagayama: "High affinity binding of thyrotropin(TSH)and Thyroid-stimulating auto antibody for the TSH receptor extra cellular domain" Thyroid. 4. 155-159 (1994)

[Publications] Yuji Nagayama: "Exacerbation of thyroid autoimmunity by interferon α treatment in patients with chronic viral hepatitis: our studies and review of the literature" Endocrine Journal. 41. 565-572 (1994)

[Publications] Wentian Luo: "Immunohistochemical analysis of expression of nm23-H1/nucleoside diphosphate kinase in human thyroid careinomas: lack of correlation between its expression and lymph node metastasis" Thyroid. 3. 105-109 (1993)

[Publications] Wentian Luo: "Taql polymorphism in the human thyrotropin receptor gene(TSHR)" Hum Mol Genet. 2. 826- (1993)

[Publications] Hiroyuki Namba: "Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes" J Endocrinol Invest. 16. 87-93 (1993)

[Publications] Yuji Nagayama: "In vivo effect of gold compounds on thyroxine to triiodothyronine conversion by typeI5´-deiodinase in patients with rheumatoid arthritis" Horm Metab Res. 25. 657-658 (1993)

[Publications] Hiroyuki Namba: "Evidence of thyroid volume increase in normal subjects receiving excess iodide" J Clin Endocrinol Metab. 76. 605-608 (1993)

[Publications] Kazuya Eishima: "The significance of^<131>I treatment of metastatic thyroid carcinoma" Int J Oncol. 2. 877-882 (1993)

[Publications] Masako Tsuruta: "Long-term follow-up studies on iodine-131 treatment of hyperthyroid Graves´disease based on the measurement of thyroid volume by ultrasonography" Ann Nucl Med. 7. 193-197 (1993)

横山直方長崎大学, 医学部, 助手 (10240219)