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  The octadecaneuropeptide-induced response of corticotropin-releasing hormone messenger RNA levels is mediated by GABAA receptors and modulated by endogenous steroids

Givalois, L., Grinevich, V., Li, S., Garcia−de−Yebenes, S. E., & Pelletier, G. (1998). The octadecaneuropeptide-induced response of corticotropin-releasing hormone messenger RNA levels is mediated by GABAA receptors and modulated by endogenous steroids. Neuroscience, 85(2), 557-567. doi:10.1016/S0306-4522(97)00650-7.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-A4A8-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-A240-9
Genre: Journal Article

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Neurosci_85_1998_557.pdf (Any fulltext), 372KB
 
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 Creators:
Givalois, L., Author
Grinevich, Valery1, 2, Author              
Li, Songyun, Author
Garcia−de−Yebenes, S. E., Author
Pelletier, Georges, Author
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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: CRH mRNA; octadecaneuropeptide; GABAA receptor; adrenal and sexual steroids; neurosteroids; hypothalamo-pituitary-adrenocortical axis
 Abstract: The involvement of endogenous benzodiazepine octadecaneuropeptide in the regulation of corticotropin-releasing hormone messenger RNA expression has been studied using in situ hybridization technique. Intracerebroventricular injection of octadecaneuropeptide (4 microg/kg) induced a 26% decrease in the corticotropin-releasing hormone messenger RNA expression in the hypothalamic paraventricular nucleus. Concomitant injection of octadecaneuropeptide and i.p. injection of the GABA(A) receptor agonist muscimol (4 mg/kg) potentiated the corticotropin-releasing hormone messenger RNA decrease ( - 34%). The depressing effect of octadecaneuropeptide on corticotropin-releasing hormone gene expression was totally reversed by pretreatment of the animals with the GABA(A) receptor antagonist picrotoxin (5 mg/kg; i.p.) or by pretreatment with the benzodiazepine receptor antagonist flumazenil (4 mg/kg; i.p.). To determine the reciprocal involvement of adrenal and sexual steroids in this regulation, animals are adrenalectomized and/or castrated. Adrenalectomy reversed the effect induced by octadecaneuropeptide, which increased corticotropin-releasing hormone messenger RNA expression (+21%), while castration did not modify the negative influence of octadecaneuropeptide. When rats were adrenalectomized and castrated, the adrenalectomy influence was predominant, since octadecaneuropeptide increased significantly the hybridization signal (+18%). The involvement of neurosteroids, especially reduced metabolites of progesterone was also investigated. The concomitant injection of octadecaneuropeptide and subcutaneous injection of the 5alpha-reductase inhibitor MK-906 (14 mg/kg) to adrenalectomized and castrated rats, reduced significantly by 60% the increase of corticotropin-releasing hormone messenger RNA expression induced by octadecaneuropeptide. These results indicate that in vivo the endogenous benzodiazepine octadecaneuropeptide, via an activation of the benzodiazepine sites of the GABA(A) receptor, negatively modulates corticotropin-releasing hormone neuronal activity and that this modulation can be negatively or positively influenced by central and peripheral steroids.

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Language(s): eng - English
 Dates: 19971997-11-241998-09-041998-04-08
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
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Title: Neuroscience
Source Genre: Journal
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Publ. Info: Oxford : Pergamon
Pages: - Volume / Issue: 85 (2) Sequence Number: - Start / End Page: 557 - 567 Identifier: ISSN: 0306-4522
CoNE: https://pure.mpg.de/cone/journals/resource/954925514498