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1998 Fiscal Year Final Research Report Summary

Study on the gene abnormalities that cause glucocorticoid-resistant POMC gene expression in corticotroph adenoma cells Cushing's disease

Research Project

Project/Area Number 09671016
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionHirosaki University

Principal Investigator

SUDA Toshihiro  Hirosaki University School of Medicine, Department of Medicine, Professor, 医学部, 教授 (30075452)

Project Period (FY) 1997 – 1998
KeywordsCushing's disease / Pituitary adenoma / POMC / protooncogene / gene abnormality / CRF / CRF receptor
Research Abstract

To clarity the mechanism of hypersecretion of ACTH and the resistance of ACTH secretion to glucocorticoid, (1) gene expression of c-fos, (2) gene expression of CRF-R1, (3) response of ACTH to DDAVP and characterization of Vi b mRNA were studied in ACTH-producing pituitary adenoma cells.
(1) c-f os Gene expression of c-fos in corticotroph adenoma cells was greater than that in non-adenoma cells. There were 2 point mutations (somatic mutation) at 5'-UTR in c-fos gene. Fos seems to bind to OR and inhibit OR-induced suppression of POMG gene expression. In addition, Fos may stimulate POMO gene expression.
(2) CRF-R1 mRNA levels were down-regulated by CRF in corticotrophs, but were up-regulated by CRF in corticotroph adenoma cells. These CRF-induced down- and up-regulation of CRF-R1 mRNA levels were mediated by cAMP.VP and glucocorticoid down-regulated CRF-RI mRNA levels in both types of ACTH cells.
(3) DDAVP, V2-agonist, stimulated ACTH secretion from corticotroph adenoma cells, but did not stimulate it in normal ACTH cells. Vib mRNA levels in corticotroph adenoma cells increased after stimulation of VP and CRF.The size of Vib mRNA in adenoma cells was similar to that of authentic V1 b mRNA.
(4) Saikosaponin and serotonin stimulated GRF gene expression in the paraventricular nucleus of the hypothalamus in rats.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Sakai, Y: "Corticotropin-releasing factor up-regulates its own receptor gene-expression in corticotropic adenoma cells in-vitro" J.Clin.Endocrinol.Metab.82. 1229-1234 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tozawa, F.: "Saireito decreases inhibitory effect of prednisolone and accelerates the recovery of rat hypothalamic-pituitary-adrenal axis" Endocrine Journal. 45. 69-74 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kagayama, K: "Serotunin stimulates corticotropin-releasing factor gene expression in the hypothalamic piraventricular roccleus of conscious rats" Neuroscience Letters. 243. 17-20 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Habu, S: "Different roles of brain IL-I in the ACTH response to central versus peripheral administration of liropolysaccharide in the rat" Cytokine. 10. 390-394 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, H: "Evidence that a fast, rate-sensitive negative feedback effect corticosterone is not a principal mechanism underlying the indomethacin inhibition of interleukin-beta-induced adrenocorticotropin secretion in the rat" Cytokine. 10. 377-381 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakai, K: "The genomic organization of the human corticotropin-releasing factor type-1 receptor" Gene. 219. 125-130 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 須田 俊宏(分担執筆): "内分泌・代謝疾患, 執筆項目「プレクリニカル クッシング症候群」" 中山書店, 419(402-406) (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堀場伸郎, 須田俊宏(分担執筆): "ストレスとホルモン, 執筆項目「プロオピオメラノ, ルチル遺伝子の発現判断」" 学会出版センター, 245(37-50) (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Sakai, N.Horiba, T.Suda et al: "CRF up-regulates its own receptor gene expression in corticotropic adenoma cells in vitro." J.Clin.Endocrinol.Metab.82(4). 1229-1234 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Suda: "Preclinical Cushing's syndrome and ACTH-independent bilateral adrenocortical macronodular hyperlasia." Internal Medicine. 36(9). 601-601 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Sakai, N.Horiba, T.Suda et al.: "Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing's syndrome." Endocrine J.44(5). 687-695 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] F.Tozawa, I.Dobashi, m T.Suda et al.: "Saireito(Chinese herbal drug)decreases inhibitory effect of prednisolone and accelerates the recovery of rat hypothalamic-pituitary-adrenal axis." Endocrine J. 45(1). 69-74 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kageyama, F.Tozawa, T.Suda et al.: "Serotonin stimutates CRF gene expression in the hypothalamic paraventricular nucleus of conscious rats." Neurisci.Lett. 243. 17-20 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Habu, H.Watanabe, T.Suda, et al.: "Different roles of brain interleukin-1 in the ACTH response to central versus peripheral administration of LPS in the rat." Cytokine. 10(5). 390-394 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Waranobe, R.Nasusita, T.Suda et al.: "Evidence that a fast, rate-sensitive negative feedback effect of corticosterone is not a principal mechanism underlying the interlrukin-1 beta-inducedACTHsecretionintherat." Cytokine. 10(5). 377-381 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Sakai, M.Yamada, T.suda et al.: "The genomic organization of the human CRF type-1 receptor." Gene. 219. 125-130 (1998)

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

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Published: 1999-12-08  

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