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1997 Fiscal Year Final Research Report Summary

A study on the regulatory mechanism of the hypothalamo-pituitary-adrenal axis

Research Project

Project/Area Number 08671127
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

WATANOBE Hajime  Hirosaki University University Hospital ; Associate Professor, 医学部附属病院, 講師 (00220947)

Project Period (FY) 1996 – 1997
KeywordsCytokine / ACTH / Lipopolysaccharide / Prostaglandin / Indomethacin
Research Abstract

1.It is known that systemic administration of lipopolysaccharide (LPS) stimulates the synthesis and secretion of various proinflammatory cytokines in both the general circulation and the brain. Thus, the relative contribution of peripheral and central cytokines to the activation of the corticotropin-releasing hormone (CRH) -adrenocorticotropin (ACTH) system is still poorly understood. In the present research project, this principal investigator attempted to examine this unresolved issue in more details. The results I obtained suggested that tumor necrosis factor (TNF) -alpha in the general circulation may play the most important role in triggering the early, peak phase of ACTH secretion after systemic LPS treatment in the rat.
2.It has been repeatedly reported that indomethacin suppress the ACTH response to interleukin (IL) -1beta in the rat. Although this finding was construed as suggesting a stimulatory role of prostaglandins in mediating the hormonal response, a group of investigators have reported that this may not be the case. In the present study, this principal investigator attempted to clarify this issue, and found that the suppression by indomethacin of the IL-1beta-induced ACTH response is mediated by indomethacin's inherent pharmacological activity, i.e.the suppression of prostaglandin production.
3.Utilizing IL-1 receptor antagonist which blocks the biological activity of IL-1, this proncipal investigator examined the involvement of brain IL-1 in mediating the ACTH response to intravenous or intracerebroventricular administration of LPS in the rat. Implications deriving from this study were that IL-1 in the brain may play an important role in mediating the ACTH secretion after intracerebroventricular, but not intravenous, administration of LPS in the rat.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Waranobe, H.: "Effcts of gender and gonadectomy on ACTH response to interleukin-1β in the rat:Comparison with the modulation of ACTH response to immobilization stress." Neuroimmunomodulation. 3. 254-258 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nasushita, R.: "A compartive study of adrenocorticotropin-releasing activity of prostaglandins E_1,E_2,F_<2a>,and D_2 in the rat." Prostaglandins,Leukotrienes,and Essen tial Faityacids. 56. 165-168 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanobe, H.: "Evidence that a fast rate-sensitive negative feedback effeck of corticosterone is not a principal mechanism underlying the indomethacin inhibition of interleukin-1β-induced adrenocorticotropin secretion in the rat." Cytokine. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Habu, S.: "Different roles of brain interkeukin-1 in the adrenocorticotropin administration of lipopolysaccharide in the rat." Cytokine. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanobe, H.: "Effects of gender and gonadectomy on ACTH response to interleukin-1beta in the rat : Comparison with the modulation of ACTH response to immobilization stress." Neuroimmunomodulation. 3. 254-258 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nasushita, R.: "A comparative study of adrenocorticotropin-releasing activity of prostaglandins E_1, E_2, F_2alpha, and D_2 in the rat." Prostaglandins, Leukotrienes, and Essential Fatty Acids. 56. 165-168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanobe, H.: "Evidence that a fast, rate-sensitive negative feedback effect of corticosterone is not a principal mechanism underlying the indomethacin inhibition of interleukin-1beta-induced adrenocorticotropin secretion in the rat." Cytokine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Habu, S.: "Different roles of brain interleukin-1 in the adrenocorticotropin response to central versus peripheral administration of lipopolysaccharide in the rat." Cytokine. (in press).

    • 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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