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1997 Fiscal Year Final Research Report Summary

Transcriptional regulation of steroidogenic P450 genes.

Research Project

Project/Area Number 07044277
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field 内分泌・代謝学
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

NAWATA Hajime  Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (10038820)

Co-Investigator(Kenkyū-buntansha) MOROHASHI Kenishirou  Okazaki National Research Institutes, National Institute for Basic Biology, Prof, 基礎生物学研究所, 教授 (30183114)
IKUYAMA Showichiro  Kyushu University, Faculty of Medicine, Research Associate, 医学部, 助手 (20184393)
YANASE Toshihiko  Kyushu University, Faculty of Medicine, Research Associate, 助手 (30239818)
TAKAYANAGI Ryoichi  Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30154917)
WATERMAN Mic  バンダービルト大学, 医学部, 教授
WATERMAN Michael R  Vanderbilt University, School of Medicine, Biochemistry, Chairman
Project Period (FY) 1995 – 1997
Keywordssteroid hormone / transcription factor / P450 / steroidogenic factor 1 / DAX-1 / Ad4BP / congenital adrenal hypoplasia / sex differentiation
Research Abstract

1. Analyzes of the transcription factors for steroidogenic P450 genes. (1) Cloning of human Ad4BP (SF-1) gene and cDNAs for CRS1-BP and E box binding protein. The size of human Ad4BP gene was about 30kb containing 7 exons, encoding 461 amino acids. E box, which was shown to be essential for transcription of Ad4BP gene, was present in the promoter region of human Ad4BP gene. CRS1-BP,a factor for cAMP responsiveness of CYP17 gene, was shown to be PbX-1. A cDNA for E box binding protein was isolated from neonatal rat testis. (2) Effects of Ad4BP and DAX-1 on the transcription of P450 gens. Ad4BP enhanced the transcription of P450SCC,P45011beta and P45017alpha genes, but DAX-1 suppressed. Ad4BP and DAX-1 thus interact each other.
2. Analyzes of Ad4BP and DAX-1 genes in congenital adrenal hypoplasia (CAH). Six males with CAH had the mutations in their DAX-1 genes : one was missense mutation and the other five were nonsense mutations due to stop codon or frame shift, and in one family, the parents of one male patient had no mutations in DAX-1 gene, indicating that CAH due to DAX-1 mutation can originate from a germ linen mutation. Three females with CAH,however, had mutation neither in Ad4BP nor DAX-1 gene, suggesting that unidentified factor (s) other than Ad4BP or DAX-1 still exists as the cause of CAH.

  • Research Products

    (73 results)

All Other

All Publications (73 results)

  • [Publications] Okabe T.et al.: "Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human lymphocytes" J.Clin.Endocrinol.Metab.80. 2993-2996 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okabe T.et al.: "cDNA cloning of a NGF1-B/nur-77 related transcription factor from an apoptotic human T cell line" J.Immunol.154. 3871-3879 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoda K.et al.: "Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonodotroph in the Ftz-F1 disrupted mice" Develop.Dynam.204. 22-29 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayama K et al.: "Immunohistochemical localization of Ad4-binding protein with correlation to steroidogenic enzyme expression in cycling human ovaries and sex cord stromal tumors" J.Clin.Endocrinol.Metab.80. 2815-2821 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.et al.: "Ad4BP in the human adrenal cortex and its disorders" Endocrinol Metab.80. 2378-2380 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Michael M.D. et al.: "Ad4BP/SF-1 regulates cyclic AMP-induced transcription from the proximal promoter(Pll) of the human aromatase P450(CYP19)gene in the ovary" J. Biol.Chem.270. 13561-13566 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomura M. et al.: "An E box element is required for the expression of the ad4bp gene, a mammalian homologue of ftz-f1 gene, which is essential for adrenal and gonadal development" J.Biol.Chem.270. 7453-7461 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanase T.et al.: "New mutation of DAX-1 gene in two Japanese patients with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism" J.Clin.Endocrinol.Metab.81. 530-535 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomura M.et al.: "Autoregulatory loop in the regulation of the mammalian ftz-fl gene" J.Biol.Chem.271. 8243-8249 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imasaki K.et al.: "Androgen insensitivity syndrome due to mutations in the DNA-binding domain of the androgen receptor" Mol.Cell.Endocrinol.120. 15-24 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imasaki K.et al.: "Sporadic Reifenstein syndrome due to a de novomutation(^<746>Val→Met) of the androgen receptor" Clin.Pediatr.Endocrinol.5. 1-9 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nawata H.et al.: "Abnormalities of sex differetation" Horm. Res.46(suppl 1). 15-19 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nawata H.et al.: "Androgen insensitivity syndrome" Frontiers in Endocrinology. 17. l07-117 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka S.et al.: "l.25-dihydroxyvitamin D^3 enhances the enzymatic activity and expresssion of the messenger nbonucleic acid for aromatase cytochreme P450 symergistically with dexamethasone depending on the Vitamin D receptor level in cultured human osteoblasts" Endocrinology. 137. 1860-1869 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oba K. et al.: "Structural characterization of human Ad4BP(SF-1)gene" Biochem.Biophys.Res.Commun.226. 261-267 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanase T.et al.: "Excpression of sterol carrier protein2(SCP2)in human adrenocortical tissue" Eur. J.Endocrinol.l34. 501-507 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniguchi S. et al.: "Dehydroepiandrosterone markedly inhibits the accumulation of cholesteryl ester in mouse macrophage J774-1 cells" Atherosclerosis.126. 143-154 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikuyama S. et al.: "Follicle stimulating hormone-β subunit gene is expressed in parallel with a transcription factor Ad4BP/SF-1 in human pituitary adenomas" Clin.Endocrinol.45. 187-193 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohe K. et al.: "Interferon-γ suppresses thyrotropin recepter promoter activity by reducing thyroid transcription factor-1(TTF-1)binding to its recognition site" Mol. Endocrinol.10. 826-836 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hatana O. et al.: "Identical origin of adrenal cortex and gonad revealed by expression profiles of Ad4BP/SF-l" Genes to Cells. 1. 663-671 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kagawa N. et al.: "A cAMP-regulatory sequence(CRS1)of CYP17 is a cellular target for the homeodomain protein Pbxl" J.Biol.Chem.269. 18716-18719 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 諸橋 憲一郎: "生殖腺の性分化とAd4BP/SF-l" 蛋白質 核酸 酵素. 41(8). l033-l041 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogo A.et al.: "cAMP-depencient transactivation involving the homeodomain protein Pbx1" Archives of Biochemistry and Biophysics. 338. 193-220 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogo A. et al.: "The homeodomain protein Pbxl is involved in cAMP-dependent transcription of human CYP17^1" Archives of Biochemistry and Biophysics. 348. 226-231 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Leers-Sucheta S.et al: "Synergistic activation of the human typeH3 β-hydroxyteroid dehydrorenase/D5D4 isomerase promoter by the transcription factcr steroidogenic factor- 1/adrenal 4-binding protein ardphorbol ester" J.Biol.Chem.272. 7960-7967 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lund J.et al.: "Transcriptional regulation of the bovine CYP17 gene by cAMP" Steroid. 62. 43-45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mason J.I. et al.: "The regulation of 3b-hydroxysteroid dehydrogenase expression" Steroid. 62. l64-168 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morohashi K.: "The ontogenesis of the steroidogenic tissues" Genes to Cells. 2. 95-106 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kakiki M.et al.: "Expression of aldosterone synthase cytcchrome P450(P450aldo)mRNA in ratadrenal glomerulosa cells by angiotensin II type receptor" Endocne Res.23(4). 277-289 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bassett M.H.: "Sequence and developmental expression of cypl8, a member of a new cytochrome P450 family from drosophlla" Mol.Cell.Endo.131. 39-49 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Vianello S. et al.: "Developmentally regulated expression and activity of 17 α-hydroxylase/C-17,20 lyase cytochrome P450 in rat liver" Endodrinology. 138. 3166-3174 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Pikuleva I.A. et al.: "Expression, purification and enzymatic properties of recombinant human cytochrome P450c27(CYP27)" Arch.Biochem.Biophys.343. 123-130 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jenkins C.M. et al.: "Escherichia coli flavodoxin sepharose as an affinity resin for cytochromes P450 and use to interaction" Arch.Biochem.Biophys.347. 93-102 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jenkins C.M. et al.: "Negatlvely-charged anabaena flavodoxin residues(Asp-144 and Glu-145)are important for reconstitution of cytochrome P450cl7 hydroxylase activity" J.Biol.Chem.272. l22509-122513 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Waterman M.R. et al.: "Diversity of ACTH (cAMP)-dependent transcription of bovine steroid hydroxylase genes" FASEB J.11. 419-427 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Waterman M.R. et al.: "Steroidogenesis, StAR, PBR:Is there light at the end of the tunnel?" Proceedings of the Society for experirmental Biology and Medicine. 217. 121-122 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue H.et al.: "A rare case of 46,XX true hermaphroditism with hidden mosaicism with SRY-bearing cells in the gonads" Internal Medicine. (in pess). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okabe T.et al.: "Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human lymphocytes" J.Clin.Endocrinol.Metab.80. 2993-2996 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okabe T.et al.: "cDNA cloning of a NGF1-B/nur-77 related transcription factor from an apoptotic human T cell line" J.Immunol.154. 3871-3879 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoda K.et al.: "Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonodotroph in the Ftz-F1 disrupted mice" Develop.Dynam.204. 22-29 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takayama K et al.: "Immunohistochemical localization of Ad4-binding protein with correlation to steroidogenic enzyme expression in cycling human ovaries and sex cord stromal tumors" J.Clin.Endocrinol.Metab.80. 2815-2821 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sasano H.et al.: "Ad4BP in the human adrenal cortex and its disorders" Endocrinol Metab.80. 2378-2380 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Michael M.D.et al.: "Ad4BP/SF-1 regulates cyclic AMP-induced transcription from the proximal promoter (PII) of the human aromatase P450 (CYP19) gene in the ovary" J.Biol.Chem.270. 13561-13566 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomura M.et al.: "An E box element is required for the expression of the ad4bp gene, a mammalian homologue of ftz-f1 gene, which is essential for adrenal and gonadal development" J.Biol.Chem.270. 7453-7461 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanase T.et al.: "New mutation of DAX-1 gene in two Japanese patients with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism" J.Clin.Endocrinol.Metab.81. 530-535 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomura M.et al.: "Autoregulatory loop in the regulation of the mammalian ftz-f1 gene" J.Biol.Chem.271. 8243-8249 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imasaki K.et al.: "Androgen insensitivity syndrome due to mutations in the DNA-binding domain of the androgen receptor" Mol.Cell.Endoctinol.120. 15-24 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imasaki K.et al.: "Sporadic Reifenstein syndrome due to a de novo mutation (746 Val*Met) of the androgen receptor" Clin.Pediatr.Endocrinol.5. 1-9 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nawata H.et al.: "Abnormalities of sex defferetation" Horm.Res.46 (suppl1). 15-19 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nawata H.et al.: "Androgen insensitivity syndrome" Frontiers in Endocrinology. 17. 107-117 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka S.et al.: "1,25-dihydroxyvitamin D^3 enhances the enzymatic activity and expression of the messenger ribonucleic acid for aromatase cytochrome P450 symergistically with dexamethasone depending on the Vitamin D receptor level in cultured human osteoblasts" Endocrinology. 137. 1860-1869 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oba K.et al.: "Structural characterization of human Ad4BP (SF-1) gene" Biochem.Biophys.Res.Commun.226. 261-267 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanase T.et al.: "Expression of sterol carrier protein2 (SCP2) in human adrenocortical tissue" Eur.J.Endocrinol.134. 501-507 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi S.et al.: "Dehydroepiandrosterone markedly inhibits the accumlation of cholesteryl ester in mouse macrophage J774-1 cells" Atherosclerosis.126. 143-154 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikuyama S.et al.: "Follicle stimulating hormone-beta subunit gene is expressed in parallel with a transcription factor Ad4BP/SF-1 in human pituitary adenomas" Clin.Endocrinol.45. 187-193 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohe K.et al.: "Interferon-gamma suppresses thyrotropin receptor promoter activity by reducing thyroid transcription factor-1 (TTF-1) binding to its recognition site" Mol.Endocrinol.10. 826-836 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hatana O.et al.: "Identical orgin of adrenal cortex and gonad revealed by expression profiles of Ad4BP/SF-1" Genes to Cells. 1. 663-671 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kagawa N.et al.: "A cAMP-regulatory sequence (CRS1) of CYP17 is a cellular target for the homeodomain protein Pbx1" J.Biol.Chem.269. 18716-18719 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogo A.et al.: "cAMP-dependent transactivation involving the homeodomain protein Pbx1 Archives of Biochemistry and Biophysics 338 : 193-220,1997" Archives of Biochemistry and Biophysics. 338. 193-220 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogo A.et al.: "The homeodomain protein Pbx1 is involved in cAMP-dependent transcription of human CYP171" Archives of Biochemistry and Biophysics. 348. 226-231 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Leers-Sucheta S.et al.: "Synergistic activation of the human typeII3beta-hydroxyteroid dehydrogenase/D5D4 isomerase promoter by the transcription factor steroidogenic factor-1/adrenal4-binding protein andphorbol ester" J.Biol.Chem.272. 7960-7967 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lund J.et al.: "Transcriptional regulation of the bovine CYP17 gene by cAMP" Steroid. 62. 43-45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mason J.I.et al.: "The regulation of 3b-hydroxysteroid dehydrogenase expression" Steroid. 62. 164-168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morohashi K.: "The ontogenesis of the steroidogenic tissues" Genes to Cells. 2. 95-106 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakiki M.et al.: "Expression of aldosterone synthase cytochrome P450 (P450aldo) mRNA in ratadrenal glomerulosa cells by angiotensin II type receptor" Endocrine Res.23 (4). 277-295 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Bassett M.H.: "Sequence and developmental expression of cyp18, a member of a new cytochrome P450 family from/drosophlla" Mol.Cell.Endo.131. 39-49 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Vianello S.et al.: "Developmentally regulated expression and activity of 17alpha-hydroxylase/C-17,20 lyase cytochrome P450 in rat liver" Endocrinology. 138. 3166-3174 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Pikuleva I.A.et al.: "Expression, purification and enzymatic properties of recombinant human cytochrome P450c27 (CYP27)" Arch.Biochem.Biophys.343. 123-130 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jenkins C.M.et al.: "Escherichia coli flavodoxin sepharose as an affinity resin for cytochromes P450 and use to interaction" Arch.Biochem.Biophys.347. 93-102 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jenkins C.M.et al.: "Negatlvely-charged anabaena flavodoxin residues (Asp-144 and Glu-145) are important for reconstitution of cytochrome P450c17 hydroxylase activity" J.Biol.Chem.272. 122509-122513 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Waterman M.R.et al.: "Diversity of ACTH (cAMP) -dependent transcription of bovine steroid hydroxylase genes" FASEB J.11. 419-427 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Waterman M.R.et al.: "Steroidogenesis, StAR,PBR : Is there light at the end of the tunnel?" Proceedings of the Society for experimental Biology and Mdicine. 217. 121-122 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue H.et al.: "A rare case of 46, XX true hermaphroditism with hidden mosaicism with SRY-bearing cells in the gonads" Internal Medicine. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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