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1994 Fiscal Year Final Research Report Summary

A study on the cytokine regulation of the hypothalamo-pituitary-adrenal system in the rat

Research Project

Project/Area Number 04671456
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionHIROSAKI UNIVETSITY

Principal Investigator

WATANOBE Hajime  Hirosaki University Hospital, Instructor, 医学部・附属病院, 講師 (00220947)

Project Period (FY) 1992 – 1994
KeywordsCytokine / ACTH / Prostaglandin / CRH / AVP / Neuropeptide
Research Abstract

A growing body of evidence suggests that various cytokines produced by activated immune cells during bacterial infection are able to stimulate the hypothalamo-pituitary-adrenal (HPA) axis in humams and animals. However, there are a great number of as yet unanswered problems in this area of research. In this study, we conducted a couple of experiments in rats to have a better understanding of the cytokine regulation of the HPA axis in this species. Specific experiments performed in the present study and implications obtained from each of them are summarized below.
(1)Utilizing the technique of push-pull perfusion (PPP) of the brain, we examined the site of action of interleukin (IL) -1beta within the corticotropinreleasing hormone (CRH) neuronal system. We obtained the data suggesting that IL-1beta may act on both the paraventricular nucleus (PVN,the site where CRH neuronal cell bodies are localized) and the median eminence (ME,the site where axonal fibers of CRH neurons are terminated). … More It was also suggested that not only CRH but arginine vasopressin (AVP) may mediate the IL-1beta stimulation of ACTH secretion.
(2)Utilizing the PPP method again, we examined the alleged significant role of prostaglandin (PG) E_2 in the IL-1beta stimulation of ACTH secretion. After an intravenous administration of IL-1beta, a significant rise in PGE_2 was observed in the PVN but not in the ME or the preoptic area of the hypothalamus.
The increase in PGE_2 in the PVN was in synchrony with the rise in CRH and AVP levels in the same hypothalamic area. These results strongly suggest that PGE_2 in the PVN may be a trigger for the activation of CRH neurons, which then leads to ACTH secretion.
Utilizing the technique of immunoneutralization of brain neuropeptides, we examined if other ACTH secretagogues such as oxytocin (OT), angiotensin II(A II), and cholecystokinin (CCK)-8, are also involved in the ACTH response induced by intracerebroventricular (icv) administration of IL-1beta. Through examining the effects of icv injection of antisera against these peptides, we obtained the data suggesting that A II,but not OT or CCK-8, may mediate the IL-1beta stimulation of ACTH secretion. In addition, utilizing the same technique, we examined whether CRH and AVP contribute to the ACTH response induced by icv injection of IL-6 and tumor necrosis factor (TNF)-alpha. It was suggested that IL-6-induced ACTH response may be mediated by both CRH and AVP, whereas the ACTH response to TNF-alpha only via CRH. Less

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Watanobe,H.: "Intrahypothalamic perfusion with interleukin-1-beta stimulates the local release of・・・" Neuroendocrinology. 57. 593-599 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanobe,H.: "Effects of intravenous administration of interleukin-1-beta on the release of・・・" Neroendocrinology. 60. 8-15 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanobe, H.: "Intrahypothalamic perfusion with interleukin-1-beta stimulates the local release of cortico-tropin-releasing hormone and arginine vasopressin and the plasma adrenocorticotropin in freely moving rats : A comparative perfusion of the paraventricular nucleus and the median eminence." Neuroendocrinology. 57. 593-599 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanobe, H.: "Effects of intravenous administration of interleukin-1-beta on the release of prostaglandin E_2, corticotropin-releasing factor, and arginine vasopressin in several hypothalamic areas of freely moving rats : Estimation by push-pull perfusion." Neuroendocrinology. 60. 8-15 (1994)

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

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Published: 1996-04-15  

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