Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats

Autores
Caruso, Carla Mariana; Mohn, Claudia Ester; Karara, Armando Luis; Rettori, Valeria; Watanobe, Hajime; Schiöthe, Helgi B.; Seilicovich, Adriana; Lasaga, Mercedes Isabel
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There is evidence that α-melanocyte-stimulating hormone (α-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of α-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 μg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by α-MSH (3 nmol/rat) injected 30 min before LPS. α-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of α-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of α-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by α-MSH. Both LPS and α-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and α-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of α-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 μg/ml) and LPS plus interferon-γ (IFN-γ, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-γ. This stimulatory effect was attenuated in the presence of α-MSH (5 μM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that α-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous α-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.
Fil: Caruso, Carla Mariana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Karara, Armando Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; Argentina
Fil: Rettori, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Watanobe, Hajime. International University of Health and Welfare; Japón
Fil: Schiöthe, Helgi B.. Uppsala Universitet; Suecia
Fil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; Argentina
Fil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; Argentina
Materia
ADRENAL STEROIDS
ALPHA-MELANOCYTE-STIMULATING HORMONE
CYCLOOXYGENASE
GONADOTROPINS
LIPOPOLYSACCHARIDE
MELANOCORTIN RECEPTORS
NITRIC OXIDE
NITRIC OXIDE SYNTHASE
PROLACTIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/149484
Acceder
id CONICETDig_de01a0800f6688c0d8f0f37a78e61198
oai_identifier_str oai:ri.conicet.gov.ar:11336/149484
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male ratsCaruso, Carla MarianaMohn, Claudia EsterKarara, Armando LuisRettori, ValeriaWatanobe, HajimeSchiöthe, Helgi B.Seilicovich, AdrianaLasaga, Mercedes IsabelADRENAL STEROIDSALPHA-MELANOCYTE-STIMULATING HORMONECYCLOOXYGENASEGONADOTROPINSLIPOPOLYSACCHARIDEMELANOCORTIN RECEPTORSNITRIC OXIDENITRIC OXIDE SYNTHASEPROLACTINhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3There is evidence that α-melanocyte-stimulating hormone (α-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of α-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 μg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by α-MSH (3 nmol/rat) injected 30 min before LPS. α-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of α-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of α-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by α-MSH. Both LPS and α-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and α-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of α-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 μg/ml) and LPS plus interferon-γ (IFN-γ, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-γ. This stimulatory effect was attenuated in the presence of α-MSH (5 μM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that α-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous α-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.Fil: Caruso, Carla Mariana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Karara, Armando Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; ArgentinaFil: Rettori, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Watanobe, Hajime. International University of Health and Welfare; JapónFil: Schiöthe, Helgi B.. Uppsala Universitet; SueciaFil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; ArgentinaFil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; ArgentinaKarger2004-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/149484Caruso, Carla Mariana; Mohn, Claudia Ester; Karara, Armando Luis; Rettori, Valeria; Watanobe, Hajime; et al.; Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats; Karger; Neuroendocrinology; 79; 5; 12-2004; 278-2860028-3835CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/79321info:eu-repo/semantics/altIdentifier/doi/10.1159/000079321info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:15:03Zoai:ri.conicet.gov.ar:11336/149484instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:15:03.568CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
title Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
spellingShingle Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
Caruso, Carla Mariana
ADRENAL STEROIDS
ALPHA-MELANOCYTE-STIMULATING HORMONE
CYCLOOXYGENASE
GONADOTROPINS
LIPOPOLYSACCHARIDE
MELANOCORTIN RECEPTORS
NITRIC OXIDE
NITRIC OXIDE SYNTHASE
PROLACTIN
title_short Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
title_full Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
title_fullStr Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
title_full_unstemmed Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
title_sort Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats
dc.creator.none.fl_str_mv Caruso, Carla Mariana
Mohn, Claudia Ester
Karara, Armando Luis
Rettori, Valeria
Watanobe, Hajime
Schiöthe, Helgi B.
Seilicovich, Adriana
Lasaga, Mercedes Isabel
author Caruso, Carla Mariana
author_facet Caruso, Carla Mariana
Mohn, Claudia Ester
Karara, Armando Luis
Rettori, Valeria
Watanobe, Hajime
Schiöthe, Helgi B.
Seilicovich, Adriana
Lasaga, Mercedes Isabel
author_role author
author2 Mohn, Claudia Ester
Karara, Armando Luis
Rettori, Valeria
Watanobe, Hajime
Schiöthe, Helgi B.
Seilicovich, Adriana
Lasaga, Mercedes Isabel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADRENAL STEROIDS
ALPHA-MELANOCYTE-STIMULATING HORMONE
CYCLOOXYGENASE
GONADOTROPINS
LIPOPOLYSACCHARIDE
MELANOCORTIN RECEPTORS
NITRIC OXIDE
NITRIC OXIDE SYNTHASE
PROLACTIN
topic ADRENAL STEROIDS
ALPHA-MELANOCYTE-STIMULATING HORMONE
CYCLOOXYGENASE
GONADOTROPINS
LIPOPOLYSACCHARIDE
MELANOCORTIN RECEPTORS
NITRIC OXIDE
NITRIC OXIDE SYNTHASE
PROLACTIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv There is evidence that α-melanocyte-stimulating hormone (α-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of α-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 μg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by α-MSH (3 nmol/rat) injected 30 min before LPS. α-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of α-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of α-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by α-MSH. Both LPS and α-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and α-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of α-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 μg/ml) and LPS plus interferon-γ (IFN-γ, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-γ. This stimulatory effect was attenuated in the presence of α-MSH (5 μM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that α-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous α-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.
Fil: Caruso, Carla Mariana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Karara, Armando Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; Argentina
Fil: Rettori, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Watanobe, Hajime. International University of Health and Welfare; Japón
Fil: Schiöthe, Helgi B.. Uppsala Universitet; Suecia
Fil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; Argentina
Fil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; Argentina
description There is evidence that α-melanocyte-stimulating hormone (α-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of α-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 μg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by α-MSH (3 nmol/rat) injected 30 min before LPS. α-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of α-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of α-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by α-MSH. Both LPS and α-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and α-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of α-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 μg/ml) and LPS plus interferon-γ (IFN-γ, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-γ. This stimulatory effect was attenuated in the presence of α-MSH (5 μM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that α-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous α-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.
publishDate 2004
dc.date.none.fl_str_mv 2004-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/149484
Caruso, Carla Mariana; Mohn, Claudia Ester; Karara, Armando Luis; Rettori, Valeria; Watanobe, Hajime; et al.; Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats; Karger; Neuroendocrinology; 79; 5; 12-2004; 278-286
0028-3835
CONICET Digital
CONICET
url http://hdl.handle.net/11336/149484
identifier_str_mv Caruso, Carla Mariana; Mohn, Claudia Ester; Karara, Armando Luis; Rettori, Valeria; Watanobe, Hajime; et al.; Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats; Karger; Neuroendocrinology; 79; 5; 12-2004; 278-286
0028-3835
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/79321
info:eu-repo/semantics/altIdentifier/doi/10.1159/000079321
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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