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  Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on corticotropin-releasing hormone (CRH) gene expression in the rat hypothalamic paraventricular nucleus

Grinevich, V., Fournier, A., & Pelletier, G. (1997). Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on corticotropin-releasing hormone (CRH) gene expression in the rat hypothalamic paraventricular nucleus. Brain Research, 773(1), 190-196. doi:10.1016/S0006-8993(97)01011-1.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-A56B-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-AB7A-5
Genre: Journal Article

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 Creators:
Grinevich, Valery1, 2, Author              
Fournier, Alain, Author
Pelletier, Georges, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Valery Grinevich Group, Max Planck Institute for Medical Research, Max Planck Society, ou_1497746              

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Free keywords: Pituitary adenylate cyclase-activating peptide; Corticotropin-releasing hormone; Hypothalamic paraventricular nucleus; In situ hybridization; Hypothalamo-pituitary-adrenocortical axis
 Abstract: Pituitary adenylate cyclase-activating peptide (PACAP) is a 38-amino-acid polypeptide, first isolated from hypothalamus, which directly stimulates in vitro the production of cAMP as well as the release of several pituitary hormones, such as growth hormone and luteinizing hormone. In vivo, PACAP has been shown to stimulate ACTH release. The presence of PACAP receptors in several brain areas, including the hypothalamus, suggests that this peptide might play a role as a neurotransmitter/neuromodulator and might be involved in the regulation of hypophysiotropic neurohormones. In order to study the role of PACAP on corticotropin-releasing hormone (CRH) neuron, we have investigated the effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injections of PACAP and the potent PACAP antagonist PACAP(6-38) on CRH gene expression in the hypothalamic paraventricular nucleus (PVN) in the male rat. The levels of CRH mRNA were evaluated by quantitative in situ hybridization. The i.c.v. injection of PACAP (4 microg/kg b.wt.) produced a 22% increase in the hybridization signal, an effect which was completely prevented by the concomitant injection of the PACAP antagonist (4 microg/kg b.wt.). On the other hand, the administration of the PACAP antagonist induced by itself a 40% decrease in the amounts of CRH mRNA. The i.v. injection of the same peptides (100 microg/kg. b.wt.) produced very similar results. These data strongly suggest that PACAP is involved in the positive regulation of CRH gene expression via specific central receptors and then can play a role as a neurotransmitter/neuromodulator. The effect observed after i.v. injection of PACAP also suggests that the circulating levels of PACAP can play a role in the modulation of CRH gene expression. PACAP might then be involved in the regulation of the HPA axis by a double mechanism: stimulation of CRH gene expression at the central level and direct effect on pituitary corticotrophs.

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Language(s): eng - English
 Dates: 1997-07-291998-02-131997-10-31
 Publication Status: Published in print
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
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Title: Brain Research
  Other : Brain Res.
Source Genre: Journal
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 773 (1) Sequence Number: - Start / End Page: 190 - 196 Identifier: ISSN: 0006-8993
CoNE: https://pure.mpg.de/cone/journals/resource/954926250616