1992 Fiscal Year Annual Research Report

ホルモン・レセプターの機能と病態に関する研究

Research Project

Project/Area Number	03404065
Research Institution	Kyoto University
Principal Investigator	葛谷英嗣京都大学, 医学部, 助教授 (20115835)
Co-Investigator(Kenkyū-buntansha)	中村浩淑京都大学, 医学部, 助手 (60164331) 中尾一和京都大学, 医学部, 教授 (00172263)
Keywords	インスリン受容体後異常 / MAPキナーゼ / 甲状腺ホルモン不応症 / 甲状腺ホルモン受容体 / エンドセリン / エンドセリン受容体 / エンドセリン受容体遺伝子
Research Abstract	1、インスリンのシグナル伝達とその異常。 (1)受容体後のシグナル伝達の解明。3T3-L1脂胞細胞を用いて、糖輸送担体へのシグナル伝達にMAPキナーゼの関与を示唆する成積を得た。Fao細胞を用いて、インスリンによってPI3キナーゼがインスリン受容体基質(IRS-1)と結合しその活性化が起こることを明らかにした。 (2)前年度に引き続き、インスリン受容体後異常症と思われる一家系について作用障害部位の検討を行った。Gbut4のPCR-SSCPには異常がなかった。線組芽細胞のインスリンによるブドウ糖取り込みは低下していたが、MAPキナーゼの活性化には異常がなかった。 2、甲状腺ホルモン不応症の異常T_3受容体解析本邦で発見された全身型甲状腺ホルモン不応症(GRTH)患者のT_3受容体(IR)β遺伝子の解析を行い、4例においてホルモン結合領域に点突然変異を固定した。さらに下垂体型不応症(PRTH)の患者においても、アミノ酸333番めのArgがTryに点突然変異していることを発見した。 PRTHの異常TRは、T_3結合能が著明に低下していた。PRTHのTR遺伝子異常は世界で最初の報告であり、PRTHとGRTHの発生機序に関し重要な知見を与えるものとなった。 3、ヒトの2種類のエンドセリン受容体遺伝子の全構造の解明。エンドセリン(ET)は血管内皮細胞の産生する強力な血管収縮ペプチドである。ETファミリーの臨床的意義を明らかにする目的で、ヒトの2種類のET受容体(ET-A及びET-B受容体)の遺伝子のクローニングを行い、それぞれの遺伝子の隣接領域を含む全構造及び染色体位置を明らかにした。

Research Products

(25 results)

All Other

All Publications (25 results)

[Publications] G.Inoue: "E Hects of ML-9 on the insulin stimulation of glucose transport in 3T3-L1 adipocytes" J.Biol.Chem.
[Publications] M.Okamoto: "Specilic activity of phosphatidylinositol 3-kinase is incieased by insulin secretion" Biochem J.
[Publications] S.Kano: "Preparation of ante-phosphoserine and antiphosphotheronine antibodies and thir application in the study of insulin-and EGF-induced phosorylation" Biochem Biophys Res Commun. 190. 283-288 (1993)
[Publications] H.Kuzuya: "Trial of insulin-like groroth factor I(IGF-1) therapy for patients with extreme insulin resistance syndromes" Diabetes.
[Publications] S.Sasaki: "Pituitary resistance thyroid hormone associated with a base mutation in the hormone-blinding domain of the human 3,5,3-triiodothyronine receptor" J.Clin.Endocrinol.Metab.
[Publications] T.Tagami: "Estemation of the protein content of thyroid hormone receptor 1 and 1 in rat tissues by Western blotting" Endocrinology. 132. 275-279 (1993)
[Publications] K.Tanaka: "Generalized resistance to thyroid hormone in a family:a case study" Endocrinol.Jpn.39. 553-538 (1992)
[Publications] S.Sasaki: "A point mutation of the T3 receptor 1 gene in a kindred of generalized resistance to thyroid hormone" Mol.Cell Endocrinol.84. 159-166 (1992)
[Publications] 中村浩淑: "甲状腺ホルモンレセプターの構造と機能" 医学のあゆみ. 161. 61-66 (1992)
[Publications] 中村浩淑: "甲状腺ホルモンレセプターとその異常症" 代謝. 29. 1159-1170 (1992)
[Publications] Y.Ogawa: "Molecular cloning of a non-isopeptide-selective human endothelin receptor." Biochem.Biophys.Res.Commun.178. 248-255 (1991)
[Publications] M.Yoshibayashi: "Plasma endothe in concentration in patients with pulmonary hypertension associated with congenital heat derects:evidence for increased production of endothelin in pulmonary circulation." Circulation. 84. 2280-2285 (1991)
[Publications] K.Hosoda: "Organization,structure,chromosomal assignment,and expression of the gene encoding the human endothel in-Areceptor." J.Biol.Chem.267. 18797-18804 (1992)
[Publications] T.Yoshimasa: "Identification and endothelin-induced activation of multiple extracellular signal-regulated kinasis in aortic smooth muscle cells." FEBS Lett.311. 195-198 (1992)
[Publications] H.Arai: "The human endothelin-B receptor gene-structural organization and chromosomal assignment-." J.Biol.Chin.(in press).
[Publications] M.Jougasaki: "Suppression of endothelin-1 secretion by lysophosphatedylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells." Cir.Res.71. 614-619 (1992)
[Publications] Y.Saito: "Endothelin in human plasma and culture medium of aortic endothelial cells-Detection and characterization with radioimmunoassay using monoclonal antibody-." Biochem.Biophys.Res.Commun.161. 320-326 (1989)
[Publications] Y.Saito: "Setection and character ization of endothelin-1-like immurnoreactivity in rat plasma." Biochem.Biophys.Res.Commun.163. 1512-1516 (1989)
[Publications] Y.Saito: "Increased plasma endothelin level in patients with essential hypertension." N.Eng.J.Med.322. 205- (1990)
[Publications] Y.Saito: "Application of monoclonal antibodies for endothelin to hypertensive research." Hypertension. 15. 734-738 (1990)
[Publications] G.Shirakami: "Acute pulmonary alveolar hypoxia increases lung and pladma endothelin-1 leve in conscious rats." Life Sci.48. 969-976 (1991)
[Publications] K.Hosoda: "Cloning and expression of human endothelin-1 receptor cDNA." FEBS Lett.287. 23-26 (1991)
[Publications] G.Shirakami: "Low doses of endothelin-1 inhibit atrial natriuretic peptide secretion." Endocrinology(in press).
[Publications] 中村浩淑: "新生化学実験講座第9巻ホルモン(II)" 東京化学同人, (1992)
[Publications] 中村浩淑: "情報伝達とその異常-内分泌" 羊士社, (1993)

1992 Fiscal Year Annual Research Report

ホルモン・レセプターの機能と病態に関する研究

Principal Investigator

葛谷 英嗣 京都大学, 医学部, 助教授 (20115835)

Research Products

[Publications] G.Inoue: "E Hects of ML-9 on the insulin stimulation of glucose transport in 3T3-L1 adipocytes" J.Biol.Chem.

[Publications] M.Okamoto: "Specilic activity of phosphatidylinositol 3-kinase is incieased by insulin secretion" Biochem J.

[Publications] S.Kano: "Preparation of ante-phosphoserine and antiphosphotheronine antibodies and thir application in the study of insulin-and EGF-induced phosorylation" Biochem Biophys Res Commun. 190. 283-288 (1993)

[Publications] H.Kuzuya: "Trial of insulin-like groroth factor I(IGF-1) therapy for patients with extreme insulin resistance syndromes" Diabetes.

[Publications] S.Sasaki: "Pituitary resistance thyroid hormone associated with a base mutation in the hormone-blinding domain of the human 3,5,3-triiodothyronine receptor" J.Clin.Endocrinol.Metab.

[Publications] T.Tagami: "Estemation of the protein content of thyroid hormone receptor 1 and 1 in rat tissues by Western blotting" Endocrinology. 132. 275-279 (1993)

[Publications] K.Tanaka: "Generalized resistance to thyroid hormone in a family:a case study" Endocrinol.Jpn.39. 553-538 (1992)

[Publications] S.Sasaki: "A point mutation of the T3 receptor 1 gene in a kindred of generalized resistance to thyroid hormone" Mol.Cell Endocrinol.84. 159-166 (1992)

[Publications] 中村 浩淑: "甲状腺ホルモンレセプターの構造と機能" 医学のあゆみ. 161. 61-66 (1992)

[Publications] 中村 浩淑: "甲状腺ホルモンレセプターとその異常症" 代謝. 29. 1159-1170 (1992)

[Publications] Y.Ogawa: "Molecular cloning of a non-isopeptide-selective human endothelin receptor." Biochem.Biophys.Res.Commun.178. 248-255 (1991)

[Publications] M.Yoshibayashi: "Plasma endothe in concentration in patients with pulmonary hypertension associated with congenital heat derects:evidence for increased production of endothelin in pulmonary circulation." Circulation. 84. 2280-2285 (1991)

[Publications] K.Hosoda: "Organization,structure,chromosomal assignment,and expression of the gene encoding the human endothel in-Areceptor." J.Biol.Chem.267. 18797-18804 (1992)

[Publications] T.Yoshimasa: "Identification and endothelin-induced activation of multiple extracellular signal-regulated kinasis in aortic smooth muscle cells." FEBS Lett.311. 195-198 (1992)

[Publications] H.Arai: "The human endothelin-B receptor gene-structural organization and chromosomal assignment-." J.Biol.Chin.(in press).

[Publications] M.Jougasaki: "Suppression of endothelin-1 secretion by lysophosphatedylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells." Cir.Res.71. 614-619 (1992)

[Publications] Y.Saito: "Endothelin in human plasma and culture medium of aortic endothelial cells-Detection and characterization with radioimmunoassay using monoclonal antibody-." Biochem.Biophys.Res.Commun.161. 320-326 (1989)

[Publications] Y.Saito: "Setection and character ization of endothelin-1-like immurnoreactivity in rat plasma." Biochem.Biophys.Res.Commun.163. 1512-1516 (1989)

[Publications] Y.Saito: "Increased plasma endothelin level in patients with essential hypertension." N.Eng.J.Med.322. 205- (1990)

[Publications] Y.Saito: "Application of monoclonal antibodies for endothelin to hypertensive research." Hypertension. 15. 734-738 (1990)

[Publications] G.Shirakami: "Acute pulmonary alveolar hypoxia increases lung and pladma endothelin-1 leve in conscious rats." Life Sci.48. 969-976 (1991)

[Publications] K.Hosoda: "Cloning and expression of human endothelin-1 receptor cDNA." FEBS Lett.287. 23-26 (1991)

[Publications] G.Shirakami: "Low doses of endothelin-1 inhibit atrial natriuretic peptide secretion." Endocrinology(in press).

[Publications] 中村 浩淑: "新生化学実験講座第9巻ホルモン(II)" 東京化学同人, (1992)

[Publications] 中村 浩淑: "情報伝達とその異常-内分泌" 羊士社, (1993)

葛谷英嗣京都大学, 医学部, 助教授 (20115835)

[Publications] 中村浩淑: "甲状腺ホルモンレセプターの構造と機能" 医学のあゆみ. 161. 61-66 (1992)

[Publications] 中村浩淑: "甲状腺ホルモンレセプターとその異常症" 代謝. 29. 1159-1170 (1992)

[Publications] 中村浩淑: "新生化学実験講座第9巻ホルモン(II)" 東京化学同人, (1992)

[Publications] 中村浩淑: "情報伝達とその異常-内分泌" 羊士社, (1993)