Cellular and molecular actions of testosterone in vascular system

Autores
Campelo, Adrián Esteban; Mont, Matteo; Simoncini, Tommaso; Massheimer, Virginia Laura
Año de publicación
2013
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Vascular function is regulated by various agonists including the sex steroid hormones estrogen, progesterone and androgens. In order to contribute to the knowledge of the role of androgens on vascular function, in this work we investigated the cellular and molecular actions of testosterone (T) on the regulation of cellular events involved in vascular physiology such as nitric oxide (NO) production, proliferation and migration of rat aortic endothelial cells (EC). We provide evidence that T (10-7 a 10-11M) induces an acute stimulation of NO production in EC (15 to 125% above/control, p<0.01), in a gene transcription independent manner and independently of aromatase action. The mechanism of action of the steroid involves the participation of the androgen receptor (82 vs 2% s/control, T vs T+Flutamide respectively, p<0.05), and is dependent on MAPK (4.24±1.11 vs 7.80±0.93; 4.51±0.73 vs 4.40±0.72 nmol NO/mg prot, C vs T; C+PD98059 vs T+PD98059,p<0.001) , PLC/PKC (4.25±1.10 vs 7.84±1.27; 4.62±0.87 vs 4.95±0.89 nmol NO/mg prot, C vs T; C+Chelerythrine vs T+Chelerythrine,p<0.001) and PI3K/Akt (4.30±0.83 vs 7.52±0.98; 4,82±0.77 vs 4.31±0.52 nmol NO/mg prot, C vs T -/+ LY294002) signaling pathways activation and dependent of the influx of extracellular calcium (82.6; 29.6; 23.2 % above/control, T; T+EGTA; T+Verapamil). Related to the cellular processes involved in vascular repair, we demonstrate that T promotes EC proliferation (3[H]-timidine incorporation) (17.3±1.4 vs 25.4±4.4, C vs T, p<0.05). The mitogenic action exhibited by the steroid is dependent on endothelial NO production since the proliferative effect is significantly reduced by the presence of the NOS inhibitor L-NAME. By means of wound healing essays it was also determined that T stimulates also EC migration. These results provide knowledge about vascular actions of T and the mechanisms of action involved
Fil: Campelo, Adrián Esteban. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Mont, Matteo. Università degli Studi di Pisa; Italia
Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
Fil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
10 Congress of the European Society of Gineclogy
Bruselas
Bélgica
European Society of Gineclogy
Materia
Testosterona
Aterosclerosis
Oxido Nitrico
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:11336/274393
Acceder
id CONICETDig_b8f42063eea8a75d5f88560fcde5f05d
oai_identifier_str oai:ri.conicet.gov.ar:11336/274393
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cellular and molecular actions of testosterone in vascular systemCampelo, Adrián EstebanMont, MatteoSimoncini, TommasoMassheimer, Virginia LauraTestosteronaAterosclerosisOxido Nitricohttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Vascular function is regulated by various agonists including the sex steroid hormones estrogen, progesterone and androgens. In order to contribute to the knowledge of the role of androgens on vascular function, in this work we investigated the cellular and molecular actions of testosterone (T) on the regulation of cellular events involved in vascular physiology such as nitric oxide (NO) production, proliferation and migration of rat aortic endothelial cells (EC). We provide evidence that T (10-7 a 10-11M) induces an acute stimulation of NO production in EC (15 to 125% above/control, p<0.01), in a gene transcription independent manner and independently of aromatase action. The mechanism of action of the steroid involves the participation of the androgen receptor (82 vs 2% s/control, T vs T+Flutamide respectively, p<0.05), and is dependent on MAPK (4.24±1.11 vs 7.80±0.93; 4.51±0.73 vs 4.40±0.72 nmol NO/mg prot, C vs T; C+PD98059 vs T+PD98059,p<0.001) , PLC/PKC (4.25±1.10 vs 7.84±1.27; 4.62±0.87 vs 4.95±0.89 nmol NO/mg prot, C vs T; C+Chelerythrine vs T+Chelerythrine,p<0.001) and PI3K/Akt (4.30±0.83 vs 7.52±0.98; 4,82±0.77 vs 4.31±0.52 nmol NO/mg prot, C vs T -/+ LY294002) signaling pathways activation and dependent of the influx of extracellular calcium (82.6; 29.6; 23.2 % above/control, T; T+EGTA; T+Verapamil). Related to the cellular processes involved in vascular repair, we demonstrate that T promotes EC proliferation (3[H]-timidine incorporation) (17.3±1.4 vs 25.4±4.4, C vs T, p<0.05). The mitogenic action exhibited by the steroid is dependent on endothelial NO production since the proliferative effect is significantly reduced by the presence of the NOS inhibitor L-NAME. By means of wound healing essays it was also determined that T stimulates also EC migration. These results provide knowledge about vascular actions of T and the mechanisms of action involvedFil: Campelo, Adrián Esteban. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Mont, Matteo. Università degli Studi di Pisa; ItaliaFil: Simoncini, Tommaso. Università degli Studi di Pisa; ItaliaFil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina10 Congress of the European Society of GineclogyBruselasBélgicaEuropean Society of GineclogyEuropean Society of Gineclogy2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/274393Cellular and molecular actions of testosterone in vascular system; 10 Congress of the European Society of Gineclogy; Bruselas; Bélgica; 2013; 1-1CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.esgynecology.org/activities/the-congress/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:47:38Zoai:ri.conicet.gov.ar:11336/274393instacron: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:34982025-11-05 10:47:38.442CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cellular and molecular actions of testosterone in vascular system
title Cellular and molecular actions of testosterone in vascular system
spellingShingle Cellular and molecular actions of testosterone in vascular system
Campelo, Adrián Esteban
Testosterona
Aterosclerosis
Oxido Nitrico
title_short Cellular and molecular actions of testosterone in vascular system
title_full Cellular and molecular actions of testosterone in vascular system
title_fullStr Cellular and molecular actions of testosterone in vascular system
title_full_unstemmed Cellular and molecular actions of testosterone in vascular system
title_sort Cellular and molecular actions of testosterone in vascular system
dc.creator.none.fl_str_mv Campelo, Adrián Esteban
Mont, Matteo
Simoncini, Tommaso
Massheimer, Virginia Laura
author Campelo, Adrián Esteban
author_facet Campelo, Adrián Esteban
Mont, Matteo
Simoncini, Tommaso
Massheimer, Virginia Laura
author_role author
author2 Mont, Matteo
Simoncini, Tommaso
Massheimer, Virginia Laura
author2_role author
author
author
dc.subject.none.fl_str_mv Testosterona
Aterosclerosis
Oxido Nitrico
topic Testosterona
Aterosclerosis
Oxido Nitrico
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Vascular function is regulated by various agonists including the sex steroid hormones estrogen, progesterone and androgens. In order to contribute to the knowledge of the role of androgens on vascular function, in this work we investigated the cellular and molecular actions of testosterone (T) on the regulation of cellular events involved in vascular physiology such as nitric oxide (NO) production, proliferation and migration of rat aortic endothelial cells (EC). We provide evidence that T (10-7 a 10-11M) induces an acute stimulation of NO production in EC (15 to 125% above/control, p<0.01), in a gene transcription independent manner and independently of aromatase action. The mechanism of action of the steroid involves the participation of the androgen receptor (82 vs 2% s/control, T vs T+Flutamide respectively, p<0.05), and is dependent on MAPK (4.24±1.11 vs 7.80±0.93; 4.51±0.73 vs 4.40±0.72 nmol NO/mg prot, C vs T; C+PD98059 vs T+PD98059,p<0.001) , PLC/PKC (4.25±1.10 vs 7.84±1.27; 4.62±0.87 vs 4.95±0.89 nmol NO/mg prot, C vs T; C+Chelerythrine vs T+Chelerythrine,p<0.001) and PI3K/Akt (4.30±0.83 vs 7.52±0.98; 4,82±0.77 vs 4.31±0.52 nmol NO/mg prot, C vs T -/+ LY294002) signaling pathways activation and dependent of the influx of extracellular calcium (82.6; 29.6; 23.2 % above/control, T; T+EGTA; T+Verapamil). Related to the cellular processes involved in vascular repair, we demonstrate that T promotes EC proliferation (3[H]-timidine incorporation) (17.3±1.4 vs 25.4±4.4, C vs T, p<0.05). The mitogenic action exhibited by the steroid is dependent on endothelial NO production since the proliferative effect is significantly reduced by the presence of the NOS inhibitor L-NAME. By means of wound healing essays it was also determined that T stimulates also EC migration. These results provide knowledge about vascular actions of T and the mechanisms of action involved
Fil: Campelo, Adrián Esteban. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Mont, Matteo. Università degli Studi di Pisa; Italia
Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
Fil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
10 Congress of the European Society of Gineclogy
Bruselas
Bélgica
European Society of Gineclogy
description Vascular function is regulated by various agonists including the sex steroid hormones estrogen, progesterone and androgens. In order to contribute to the knowledge of the role of androgens on vascular function, in this work we investigated the cellular and molecular actions of testosterone (T) on the regulation of cellular events involved in vascular physiology such as nitric oxide (NO) production, proliferation and migration of rat aortic endothelial cells (EC). We provide evidence that T (10-7 a 10-11M) induces an acute stimulation of NO production in EC (15 to 125% above/control, p<0.01), in a gene transcription independent manner and independently of aromatase action. The mechanism of action of the steroid involves the participation of the androgen receptor (82 vs 2% s/control, T vs T+Flutamide respectively, p<0.05), and is dependent on MAPK (4.24±1.11 vs 7.80±0.93; 4.51±0.73 vs 4.40±0.72 nmol NO/mg prot, C vs T; C+PD98059 vs T+PD98059,p<0.001) , PLC/PKC (4.25±1.10 vs 7.84±1.27; 4.62±0.87 vs 4.95±0.89 nmol NO/mg prot, C vs T; C+Chelerythrine vs T+Chelerythrine,p<0.001) and PI3K/Akt (4.30±0.83 vs 7.52±0.98; 4,82±0.77 vs 4.31±0.52 nmol NO/mg prot, C vs T -/+ LY294002) signaling pathways activation and dependent of the influx of extracellular calcium (82.6; 29.6; 23.2 % above/control, T; T+EGTA; T+Verapamil). Related to the cellular processes involved in vascular repair, we demonstrate that T promotes EC proliferation (3[H]-timidine incorporation) (17.3±1.4 vs 25.4±4.4, C vs T, p<0.05). The mitogenic action exhibited by the steroid is dependent on endothelial NO production since the proliferative effect is significantly reduced by the presence of the NOS inhibitor L-NAME. By means of wound healing essays it was also determined that T stimulates also EC migration. These results provide knowledge about vascular actions of T and the mechanisms of action involved
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/274393
Cellular and molecular actions of testosterone in vascular system; 10 Congress of the European Society of Gineclogy; Bruselas; Bélgica; 2013; 1-1
CONICET Digital
CONICET
url http://hdl.handle.net/11336/274393
identifier_str_mv Cellular and molecular actions of testosterone in vascular system; 10 Congress of the European Society of Gineclogy; Bruselas; Bélgica; 2013; 1-1
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.esgynecology.org/activities/the-congress/
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
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv European Society of Gineclogy
publisher.none.fl_str_mv European Society of Gineclogy
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
_version_ 1847978187539087360
score 13.084122

Publicaciones similares