文部科学省科学研究費特定領域研究「性分化機構の解明」 *

研究成果

柳瀬 敏彦 YANASE, Toshihiko
九州大学大学院医学研究院病態制御内科(第三内科)
研究項目A03 「性分化異常症の解析」
研究課題 性分化に及ぼす性ステロイド合成・作用系異常に関する基礎的、臨床的研究

SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells. Gondo S, Yanase T, Okabe T, Tanaka T, Morinaga H, Nomura M, Goto K , Nawata H Genes to Cells, 9, 1239-1247, 2004

研究内容概説ー我々はアデノウイルスによるSF-1の強制発現が初代長期培養骨髄細胞を、副腎皮質刺激ホルモンに反応しde novoに多様なステロイドホルモンを産生するステロイド産生細胞に変化させることを明らかにした。ステロイドホルモン欠損症に対する自己細胞移植療法への応用が期待される。 (新聞記事はこちら)

Protein kinase A potentiates Ad4BP/SF-1 transactivation by re-integrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, GCN5/TRRAP, and suppressor, DAX-1: a laser confocal imaging study in living KGN cells. Fan W, Yanase T, Yin W, Kawate H, Saitoh M, Oba K, Nomura M, Okabe T, Goto K, Yanagisawa J, Kato S, Takayanagi R, Nawata H Mol Endocrinol 18, 127-141, 2004

研究内容概説ーProtein Kinase A (PKA)の活性化は副腎・性腺の発生分化に必須のAd4BP/SF-1の転写活性を劇的に増強するが、その機序は不明である。核内受容体はリガンド結合や蛋白-蛋白相互作用によりその動的特性を変化させ、生物学的作用に影響する。我々はPKA のSF-1転写活性化促進機序を蛋白動態解析の観点から解析し、PKA 活性化はSF-1とコアクチベーター(GCN5/TRRAP)やサプレッサー(DAX-1)との相互作用を統合的に修飾し、SF-1の転写活性化をさらに増強することを明らかにした。


2006年発表論文

Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor. S. Fan, K. Goto, G. Chen, H. Morinaga, M. Nomura, T. Okabe, H. Nawata, T. Yanase Biochem. Biophys. Res. Commum. 341, 192-201, 2006

The Gly 146Ala variation in human SF-1 gene:Its association with insulin resistance and type 2 diabetes in Chinese. W. Liu, M. Liu, W. Fan, H. Nawata, T. Yanase Diabetes Res. Clin. Practice. (in press)

Serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S) in oldest old Japanese women correlate with cognitive activity rather than activities of daily living T. Yanase, K. Muta, H. Nawata Geriatrics and Gerontology Inter. (in press)

Differentiation and Regeneration of Adrenal Tissues: An Initial Step Toward Regeneration Therapy for Steroid Insufficiency T. Yanase, S. Gondo, T. Okabe, T. Tanaka, H. Shirohzu, W. Fan, K. Oba, H. Morinaga, K. Ohe, H. Nawata Endocrine J. (in press)

Modification of glucocorticoid-sensitivity by MAP kinase signaling pathways in glucocorticoid-induced T-cell apoptosis. T. Tanaka, T. Okabe, S. Gondo, M. Fukuda, M. Yamamoto, T. Umemura, K. Tani, M. Nomura, K. Goto, T. Yanase, H. Nawata Expl. Hematol. (in press)

2005年発表論文

Fan W , Yanase T, Wei L, Nomura M, Okabe T, Goto K, Harada N, Nawata H: Activation of Peroxisome Proliferator Activated Receptor g and Retinoid X ReceptorInhibits CYP19 transcription through NF-kB in Ovarian Granulosa Cells Endocrinology 146: 85-92, 2005

Fan W, Yanase T, Nomura M, Okabe T, Goto K, Sato T, Kawano H, Kato S, Nawata H: Androgen receptor null male mice develop late-onset obesity due to decreased energy expenditure and lypolytic activity but show normal insulin sensitivity with high adiponectin secretion. Diabetes 54: 1000-1008, 2005

Nishi Y, Hosoda H, Mori K, Kaiya H, Sato T, Fukue Y, Fukushima N, Yanase T, Nawata H, Kangawa K, Kojima M; Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghreln. Endocrinology 146: 2255-64, 2005

Ashida K, Goto K, Zhao Y, Okabe T, Yanase T, Takayanagi R, Nomura M, Nawata H: Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinas pathway by a novel PTPN7 locus-derived transcript. Biochem Biophys Acta 1728: 84-94, 2005

Taniyama M, Tanabe M, Saito H, Ban Y, Nawata H, Yanase T: Subtle 17a-hydroxylase/17,20-lyase deficiency with homozygous Y201N Mutation in an infertile women. J Clin Endocrinol Metab 90: 2508-11, 2005

Nagasawa E, Abe Y, Nishimura J, Yanase T, Nawata H, Muta K: Pivotal role of proxisome proliferators-activated receptor gamma (PPAR gamma) in regulation of erythroid progenitor cell proliferation and differentiation. Experimental Hematology 33:857-864, 2005.doi:10.1016/j.exphem.2005.05.003?

2004年発表論文

Fan W, Yanase T, Yin W, Kawate H, Saitoh M, Oba K, Nomura M, Okabe T, Goto K, Yanagisawa J, Kato S, Takayanagi R, Nawata H: Protein kinase A potentiates Ad4BP/SF-1 transactivation by re-integrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, GCN5/TRRAP, and suppressor, DAX-1: a laser confocal imaging study in living KGN cells. Mol Endocrinol 18: 127-141, 2004

Morinaga H, Yanase T, Nomura M, Okabe T, Goto K, Harada N, Nawata H: A Benzimidazole Fungicide, Benomyl and Its Metabolite Carbendazim Induce Aromatase Activity in Human Ovarian Granulose-Like Tumor Cell Line (KGN). Endocrinology 145: 1860-1869, 2004

岩本 晃明、 柳瀬 敏彦、 高  英哲、 堀江  均、 馬場 克幸、 並木 幹夫、 名和田 新:日本人成人男子の総テストステロン、遊離テストステロンの基準値の設定 日本泌尿器科学会雑誌 95: 751-60, 2004

Chu S, Nishi Y, Yanase T, Nawata H, Fuller PJ.: Transrepression of Estrogen Receptor {beta} Signaling by Nuclear Factor-{kappa}B in Ovarian Granulosa Cells. Mol Endocrinol. ;18:1919-1928. 2004

Gondo S, Yanase T, Okabe T, Tanaka T, Morinaga H, Nomura M, Goto K, Nawata H: SF-1/Ad4BP Transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells. Genes to Cells 9: 1239-47, 2004

Wu Y, Ghosh S, Nishi Y, Yanase T, Nawata H, Hu Y: The orphan nuclear receptor NURR1 and NGFI-B modulate aromatase gene expression in ovarian granulose cells: A possible mechanism for repression ofaromatase expression upon luteinizing hormone surge Endocrinology 146: 237-46, 2004.

Ohno,K, Araki N, Yanase T, Nawata H, Iida M: A Novel Nonradioactive Method for Measuring Aromatase Activity Using a Human Ovarian Granulosa-Like Tumor Cell Line and an Estrone ELISA. Tox Sci 82: 443-50, 2004

Nawata H, Shirasawa S, Nakashima N, Araki E, Hashiguchi J, Miyake S, Yamauchi T, Hamaguchi K, Takeda H, Fukushima H, Sasahara T, Yamaguchi K, Sonoda N, Sonoda T, Matsumoto M, Tanaka Y, Sugimoto K, Tsubouchi H, Inoguch T, Yanase T, Wake N, Narazaki K, Eto T, Umeda F, Nakazaki M, Ono J, Asano T, Ito Y, Akazawa S, Hazegawa I, Takasu N, Shinohara M, Nagafuchi S, Oketa T, Iwase M, Ishikawa M, Aoki M, Keicho N, Kato N, Yasuda K, Yamamoto K, Sasazuki T: Genome-wide linkage analysis of type 2 diabetes mellitus reconfirms the susceptibility locus on 11p13-p12 in Japanese. J Human Genetics 49: 629-34, 2004