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
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。


2008年発表論文

Ito, M., Muraki, M., Takahashi, Y., Imai, M., Tsukui, T., Yamakawa, N., Nakagawa, K., Ohgi, S., Horikawa, T., Iwasaki, W., Iida, A., Nishi, Y., Yanase, T., Nawata, H., Miyado, K., Kono, T., Hosoi, Y., Saito, H: Glutathione S-transferase theta 1 expressed in granulosa cells as a biomarker for oocyte quality in age-related infertility. Fertil Steril 90, 1026-1035, 2008

Shirohzu, H., Okabe, T., Gondo, S., Tanaka, T., Ohe, K., Morinaga, H., Kawate, H., Nomura, M., Takayanagi, R., Nawata, H., Yanase, T. : Methylation of a conserved intronic CpG island of mouse SF-1 is associated with cell-specific expression of SF-1 in a culture system but not with tissue-specific expression. Biochem Biophys Res Commun 369, 862-867, 2008

Woods, D.C., Liu, H.K., Nishi, Y., Yanase, T., Johnson, A.L. : Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death. Cancer Lett 260, 20-27, 2008

Mottershead, D.G., Pulkko, M., Muggalla, P., Pastemach, A., Tolone, M., Myllymaa, S., Korchynskyi, O., Nishi, Y., Yanase, T., Lun, S., Juengel, J., Laitinen, M., Rivos, O. : Characterizaton of human growth differntiation factor-9 signaling in ovarian granulose cells. Mol Cell Endocrinol 283, 58-67, 2008

2007年発表論文

Tanaka, T., Gondo, S., Okabe, T., Ohe, K., Shirohzu, H., Morinaga, H., Nomura, M., Tani, K., Takayanagi, R., Nawata, H., Yanase, T. : Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells. J Mol Endocrinol 39, 343-350, 2007

Fan, W., Yanase, T., Morinaga, H., Gondo, S., Okabe, T., Nomura, M., Hayes, T.B., Takayanagi, R., Nawata, H.: Herbicide atrazine activates SF-1 direct affinity and concomitant aoactivators recruitments to induces aromatase expression via promoter II. Biochem Biores Res Commun 355, 1012-1018, 2007

Fan, W., Yanase, T., Morinaga, H., Gondo, S., Okabe, T., Nomura, M., Komatsu, T., Morohashi, K., Hayes, T.B., Takayanagi, R., Nawata, H. : Atrazine-induced aromatase expression is SF-1- dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans. Enviromental Health Perspectives 117, 720-727, 2007

Miyamoto, J., Matsumoto, T., Shiina, H., Inoue, K., Takada, I., Ito, S., Itoh, J., Minematsu, T., Sato, T., Yanase, T., Nawata, H., Osamura, Y.R., Kato, S. : The pituitary function of androgen receptor constitutes a glucocorticoid production circuit. Mol. Cell Biol. 27, 4807-14, 2007

Fan, W., Yanase, T., Morinaga, H., Okabe, T., Nomura, M., Daitoku, H, Fukamizu, A., Kato, S., Takayanagi, R., Nawata, H. : IGF1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. 282, 7329-38, 2007

2006年発表論文

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

W. Liu, M. Liu, W. Fan, H. Nawata, T. Yanase. :The Gly 146Ala variation in human SF-1 gene:Its association with insulin resistance and type 2 diabetes in Chinese. Diabetes Res. Clin. Practice. 73, 322-328, 2006

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

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

T. Tanaka, T. Okabe, S. Gondo, M. Fukuda, M. Yamamoto, T. Umemura, K. Tani, M. Nomura, K. Goto, T. Yanase, H. Nawata. : Modification of glucocorticoid-sensitivity by MAP kinase signaling pathways in glucocorticoid-induced T-cell apoptosis. Expl. Hematol. 34,1542-1552,2006

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?

Kawate, H., Wu, Y., Ohnaka, K., Tao, R.-H., Nakamura, K., Okabe, T., Yanase, T., Nawata, H., Takayanagi, R. : Impaired nuclear translocation, nuclear matrix targeting and intranuclear mobility of mutant androgen receptors carring amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androen insensitivity syndrome. patients J. Clin. Endocrinol. Metab. 90, 6162-6169, 2005

Chen, G., Nomura, M., Morinaga, H., Matsubara, E., Okabe, T., Goto, K., Yanase, T., Zheng, H., Lu, J., Nawata, H. : Modulation of androgen receptor transactivation by FoxH1: A newly identified androgen receptor corepressor J. Biol. Chem. 280, 36355-63, 2005

Harris, S.E., Chand, A.L., Winship, I.M., Gersak, K., Nishi, Y., Yanase, T., Nawata, H., Shelling, A. : INHA promoter polymorphisms are associated with premature ovarian failure. Molecular Human Reproduction 11, 779-784, 2005

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