An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors

Autores
Bussmann, Ursula Agnes; Bussmann, Leonardo Edmundo; Barañao, Jose Lino Salvador
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways.
Fil: Bussmann, Ursula Agnes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bussmann, Leonardo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Barañao, Jose Lino Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Materia
Aryl Hydrocarbon Receptor
Estradiol
Estradiol Receptor
Granulosa Cells
Ovary
Toxicology
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:11336/28534
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/28534
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptorsBussmann, Ursula AgnesBussmann, Leonardo EdmundoBarañao, Jose Lino SalvadorAryl Hydrocarbon ReceptorEstradiolEstradiol ReceptorGranulosa CellsOvaryToxicologyhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways.Fil: Bussmann, Ursula Agnes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bussmann, Leonardo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Barañao, Jose Lino Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaSociety for the Study of Reproduction2006-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/28534Bussmann, Ursula Agnes; Bussmann, Leonardo Edmundo; Barañao, Jose Lino Salvador; An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors; Society for the Study of Reproduction; Biology of Reproduction; 74; 2; 2-2006; 417-4260006-3363CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biolreprod/article/74/2/417/2667045info:eu-repo/semantics/altIdentifier/doi/10.1095/biolreprod.105.043901info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/abstract/med/16237154info:eu-repo/semantics/altIdentifier/pmid/16237154info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:45Zoai:ri.conicet.gov.ar:11336/28534instacron: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:34982025-09-03 09:49:46.195CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
title An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
spellingShingle An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
Bussmann, Ursula Agnes
Aryl Hydrocarbon Receptor
Estradiol
Estradiol Receptor
Granulosa Cells
Ovary
Toxicology
title_short An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
title_full An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
title_fullStr An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
title_full_unstemmed An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
title_sort An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors
dc.creator.none.fl_str_mv Bussmann, Ursula Agnes
Bussmann, Leonardo Edmundo
Barañao, Jose Lino Salvador
author Bussmann, Ursula Agnes
author_facet Bussmann, Ursula Agnes
Bussmann, Leonardo Edmundo
Barañao, Jose Lino Salvador
author_role author
author2 Bussmann, Leonardo Edmundo
Barañao, Jose Lino Salvador
author2_role author
author
dc.subject.none.fl_str_mv Aryl Hydrocarbon Receptor
Estradiol
Estradiol Receptor
Granulosa Cells
Ovary
Toxicology
topic Aryl Hydrocarbon Receptor
Estradiol
Estradiol Receptor
Granulosa Cells
Ovary
Toxicology
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways.
Fil: Bussmann, Ursula Agnes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bussmann, Leonardo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Barañao, Jose Lino Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
description The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways.
publishDate 2006
dc.date.none.fl_str_mv 2006-02
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/11336/28534
Bussmann, Ursula Agnes; Bussmann, Leonardo Edmundo; Barañao, Jose Lino Salvador; An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors; Society for the Study of Reproduction; Biology of Reproduction; 74; 2; 2-2006; 417-426
0006-3363
CONICET Digital
CONICET
url http://hdl.handle.net/11336/28534
identifier_str_mv Bussmann, Ursula Agnes; Bussmann, Leonardo Edmundo; Barañao, Jose Lino Salvador; An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors; Society for the Study of Reproduction; Biology of Reproduction; 74; 2; 2-2006; 417-426
0006-3363
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://academic.oup.com/biolreprod/article/74/2/417/2667045
info:eu-repo/semantics/altIdentifier/doi/10.1095/biolreprod.105.043901
info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/abstract/med/16237154
info:eu-repo/semantics/altIdentifier/pmid/16237154
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
dc.publisher.none.fl_str_mv Society for the Study of Reproduction
publisher.none.fl_str_mv Society for the Study of Reproduction
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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