Mutant P450 oxidoreductase causes disordered steroidogensis with and without Antley-Bixler syndrome. Fluck C, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Medonca BB, Fujieda K, Miller WL Nat Genet 36, 228-230, 2004

研究内容概説ーAntley-Bixler症候群は、頭蓋縫合早期癒合症、特徴的な願貌、上腕骨檮骨の骨性癒合、多発性関節拘縮、外性器異常、副腎不全などを合併する先天奇形症候群である。 原因としてすでにFGFR2の異常が同定されているが、外陰部異常やステロイド産生異常を呈する本症の原因としてP450 oxidoreductase（POR)の異常であることを同定した。従って、本症の成因は二つあるが、このPORの異常により本酵素に依存するミクロゾーム酵素で あるCYP21A, CYP17A1, CYP19A1, CYP51A1などの酵素活性が低下する。これにより本症にみられる彩な症状が発現することが明らかとなった。また、ROPは薬物代謝P450酵素活性に関与することから、フルコナゾールを服用していた妊婦から本症が発症したことも説明しうる。

2009年発表論文

Tajima T, Fujiwara F, Fujieda K: A novel heterozygous mutation of steroidogenic factor-1 (SF-1/Ad4BP) gene (NR5A1) in a 46, XY disorders of sex development (DSD) patient without adrenal failure. Endocr J, in press

Fukami M, Nishimura G, Homma K, Nagai T, Hanaki K, Uematsu A, Ishii T, Numakura C, Sawada H, Nakacho M, Kowase T, Motomura K, Haruna H, Nakamura M, Ohishi A, Adachi M, Tajima T, Hasegawa Y, Hasegawa T, Horikawa R, Fujieda K, Ogata T: Cytochrome P450 Oxidoreductase Deficiency: Identification and Characterization of Biallelic Mutations and Genotype-Phenotype Correlations in 35 Japanese Patients. J Clin Endocrinol Metab. 2009, in press

2008年発表論文

Okuhara K, Abe S, Kondo T, Fujita K, Koda N, Mochizuki H, Fujieda K, Tajima T: Four Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism caused by DAX-1 gene mutations: mutant DAX-1 failed to repress steroidogenic acute regulatory protein (StAR) and luteinizing hormone beta-subunit gene promoter activity. Endocr J. 55, 97-103, 2008

2007年発表論文

Sugawara T, Nomura E, Hoshi N: Cholesterol sulphate affects production of steroid hormones by reducing steroidogenic acute regulatory protein level in adrenocortical cells. J Endocrinol. 195, 451-458, 2007

2006年発表論文

Warita K, Sugawara T, Yue ZP, Tsukahara S, Mutoh K, Hasegawa Y, Kitagawa H, Mori C, Hoshi N: Progression of the dose-related effects of estrogenic endocrine disruptors, an important factor in declining fertility, differs between the hypothalamo-pituitary axis and reproductive organs of male mice. J Vet Med Sci. 68, 1257-1267, 2006

Sugawara T, Sakuragi N, Minakami H: CREM confers cAMP responsiveness in human steroidogenic acute regulatory protein expression in NCI-H295R cells rather than SF-1/Ad4BP. J Endocrinol. 191, 339-348, 2006

Hughes IA, Houk C, Ahmed SF, Lee PA, LWPES/ESPE Consensus Group (Fujieda K, et al): Consensus statement on management of intersex disorders. Arch Dis Child. 91, 554-563, 2006

Both N-terminal and C-terminal regions of steroid sulphatase are important for enzyme activity. T. Sugawara, E. Nomura, N. Hoshi J. Endocrinol. 188, 365-374, 2006

2005年発表論文

Franzese A, Brunetti-Pierri N, Spadaro R, Mukai T, Valerio G: Inappropriate tall stature and renal ectopy in a male patient with X-linked congenital adrenal hypoplasia due to a novel missense mutation in the DAX-1 gene. Am J Med Genet. 135A, 72-74, 2005

K. Fujieda, T. Tajima : Molecular basis of adrenal insufficiency. Pediatr. Res. 57, 62-69, 2005

M. Fukami, F. Kato, T. Tajima, S. Yokoya, T. Ogata : Transactivation function of -800 bp evolutionarily conserved sequence at the SHOX 3' region. Implication for the downstream enhancer. Am. J. Hum. Genet. 78, 167-170, 2005

2004年発表論文

Sugawara T, Nomura E, Nakajima A, Sakuragi N: Characterization of binding between SF-1 and Sp1: predominant interaction of SF-1 with the N-terminal region of Sp1. J Endocrinol Invest. 27, 133-141, 2004

C.E. Fluck, T. Tajima, A.V. Pandey, W. Arlt, K. Okuhara, C.F. Verge, E.W. Jabs, B.B. Mendonca, K. Fujieda, W.L. Miller. : Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nature Genet. 36, 228-230, 2004

A.V. Pandey, C.E. Fluck, N. Huang, T. Tajima, K. Fujieda, W.L. Miller : P450 oxidoreductase deficiency: a new disorder of steroidogenesis affecting all microsomal P450 enzymes. Endocri. Res. 30, 881-888, 2004

T. Sugawara : Role of StAR binding protein in steroidogenic cells. Endocri. Res. 30, 695, 2004

Sugawara T, Hoshi N, Sakuragi N: Immunohistochemical study of steroidogenic acute regulatory (StAR) protein in ovarian tumors. The Internet Journal of Gynecology and Obstetrics. 3, 2, 2004

T. Sugawara, E. Nomura, A. Nakajima, N. Sakuragi : Characterization of binding between SF-1 and Sp1: predominant interaction of SF-1 with the N-terminal region of Sp1. J. Endocrinol. Inv. 27, 133-141, 2004