Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor

Autores
Radl, Daniela Betiana; Ferraris, Maria Jimena; Boti, Valeria Romina; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel Alberto
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.
Fil: Radl, Daniela Betiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferraris, Maria Jimena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Boti, Valeria Romina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Seilicovich, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sarkar, Dipak Kumar. State University Of New Jersey; Estados Unidos
Fil: Pisera, Daniel Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Dopamine
D2 Receptor Isoform
D2S
Cabergoline
Apoptosis
Lactotropes
Estradiol
P38 Mapk
Anterior Pituitary
Prolactinoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15174
Acceder
id CONICETDig_6f2bbd56baaed4795215f3e1cdcdcf22
oai_identifier_str oai:ri.conicet.gov.ar:11336/15174
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptorRadl, Daniela BetianaFerraris, Maria JimenaBoti, Valeria RominaSeilicovich, AdrianaSarkar, Dipak KumarPisera, Daniel AlbertoDopamineD2 Receptor IsoformD2SCabergolineApoptosisLactotropesEstradiolP38 MapkAnterior PituitaryProlactinomahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.Fil: Radl, Daniela Betiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferraris, Maria Jimena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Boti, Valeria Romina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seilicovich, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sarkar, Dipak Kumar. State University Of New Jersey; Estados UnidosFil: Pisera, Daniel Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaPublic Library of Science2011-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15174Radl, Daniela Betiana; Ferraris, Maria Jimena; Boti, Valeria Romina; Seilicovich, Adriana; Sarkar, Dipak Kumar; et al.; Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor; Public Library of Science; Plos One; 6; 3; 3-2011; 18097-181041932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018097info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0018097info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:36Zoai:ri.conicet.gov.ar:11336/15174instacron: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 09:51:37.208CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
title Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
spellingShingle Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
Radl, Daniela Betiana
Dopamine
D2 Receptor Isoform
D2S
Cabergoline
Apoptosis
Lactotropes
Estradiol
P38 Mapk
Anterior Pituitary
Prolactinoma
title_short Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
title_full Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
title_fullStr Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
title_full_unstemmed Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
title_sort Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor
dc.creator.none.fl_str_mv Radl, Daniela Betiana
Ferraris, Maria Jimena
Boti, Valeria Romina
Seilicovich, Adriana
Sarkar, Dipak Kumar
Pisera, Daniel Alberto
author Radl, Daniela Betiana
author_facet Radl, Daniela Betiana
Ferraris, Maria Jimena
Boti, Valeria Romina
Seilicovich, Adriana
Sarkar, Dipak Kumar
Pisera, Daniel Alberto
author_role author
author2 Ferraris, Maria Jimena
Boti, Valeria Romina
Seilicovich, Adriana
Sarkar, Dipak Kumar
Pisera, Daniel Alberto
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Dopamine
D2 Receptor Isoform
D2S
Cabergoline
Apoptosis
Lactotropes
Estradiol
P38 Mapk
Anterior Pituitary
Prolactinoma
topic Dopamine
D2 Receptor Isoform
D2S
Cabergoline
Apoptosis
Lactotropes
Estradiol
P38 Mapk
Anterior Pituitary
Prolactinoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.
Fil: Radl, Daniela Betiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferraris, Maria Jimena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Boti, Valeria Romina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Seilicovich, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sarkar, Dipak Kumar. State University Of New Jersey; Estados Unidos
Fil: Pisera, Daniel Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.
publishDate 2011
dc.date.none.fl_str_mv 2011-03
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/11336/15174
Radl, Daniela Betiana; Ferraris, Maria Jimena; Boti, Valeria Romina; Seilicovich, Adriana; Sarkar, Dipak Kumar; et al.; Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor; Public Library of Science; Plos One; 6; 3; 3-2011; 18097-18104
1932-6203
url http://hdl.handle.net/11336/15174
identifier_str_mv Radl, Daniela Betiana; Ferraris, Maria Jimena; Boti, Valeria Romina; Seilicovich, Adriana; Sarkar, Dipak Kumar; et al.; Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor; Public Library of Science; Plos One; 6; 3; 3-2011; 18097-18104
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018097
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0018097
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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 13.13397

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