Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression

Autores
Ferraris, Maria Jimena; Boutillon, Florence; Bernadet, Marie; Seilicovich, Adriana; Goffin, Vincent; Pisera, Daniel Alberto
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Since anterior pituitary expresses prolactin receptors, prolactin secreted by lactotropes could exert autocrine or paracrine actions on anterior pituitary cells. In fact, it has been observed that prolactin inhibits its own expression by lactotropes. Our hypothesis is that prolactin participates in the control of anterior pituitary cell turnover. In the present study, we explored the action of prolactin on proliferation and apoptosis of anterior pituitary cells and its effect on the expression of the prolactin receptor. To determine the activity of endogenous prolactin, we evaluated the effect of the competitive prolactin receptor antagonist Δ1–9-G129R-hPRL in vivo, using transgenic mice that constitutively and systemically express this antagonist. The weight of the pituitary gland and the anterior pituitary proliferation index, determined by BrdU incorporation, were higher in transgenic mice expressing the antagonist than in wild-type littermates. In addition, blockade of prolactin receptor in vitro by Δ1–9-G129R-hPRL increased proliferation and inhibited apoptosis of somatolactotrope GH3 cells and of primary cultures of male rat anterior pituitary cells, including lactotropes. These results suggest that prolactin acts as an autocrine/paracrine antiproliferative and proapoptotic factor in the anterior pituitary gland. In addition, anterior pituitary expression of the long isoform of the prolactin receptor, measured by real-time PCR, increased about 10-fold in transgenic mice expressing the prolactin receptor antagonist, whereas only a modest increase in the S3 short-isoform expression was observed. These results suggest that endogenous prolactin may regulate its own biological actions in the anterior pituitary by inhibiting the expression of the long isoform of the prolactin receptor. In conclusion, our observations suggest that prolactin is involved in the maintenance of physiological cell renewal in the anterior pituitary. Alterations in this physiological role of prolactin could contribute to pituitary tumor development.
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: Boutillon, Florence. Universite de Paris V; Francia
Fil: Bernadet, Marie. Universite de Paris V; Francia
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: Goffin, Vincent. Universite de Paris V; Francia
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
Apoptosis
Antiproliferative Effect
∆1-9-G129-Hprl
Long Prolactin Receptor
Short Prolactin Receptor
Prolactin Receptor Isoform
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:11336/15234

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network_name_str CONICET Digital (CONICET)
spelling Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expressionFerraris, Maria JimenaBoutillon, FlorenceBernadet, MarieSeilicovich, AdrianaGoffin, VincentPisera, Daniel AlbertoApoptosisAntiproliferative Effect∆1-9-G129-HprlLong Prolactin ReceptorShort Prolactin ReceptorProlactin Receptor Isoformhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Since anterior pituitary expresses prolactin receptors, prolactin secreted by lactotropes could exert autocrine or paracrine actions on anterior pituitary cells. In fact, it has been observed that prolactin inhibits its own expression by lactotropes. Our hypothesis is that prolactin participates in the control of anterior pituitary cell turnover. In the present study, we explored the action of prolactin on proliferation and apoptosis of anterior pituitary cells and its effect on the expression of the prolactin receptor. To determine the activity of endogenous prolactin, we evaluated the effect of the competitive prolactin receptor antagonist Δ1–9-G129R-hPRL in vivo, using transgenic mice that constitutively and systemically express this antagonist. The weight of the pituitary gland and the anterior pituitary proliferation index, determined by BrdU incorporation, were higher in transgenic mice expressing the antagonist than in wild-type littermates. In addition, blockade of prolactin receptor in vitro by Δ1–9-G129R-hPRL increased proliferation and inhibited apoptosis of somatolactotrope GH3 cells and of primary cultures of male rat anterior pituitary cells, including lactotropes. These results suggest that prolactin acts as an autocrine/paracrine antiproliferative and proapoptotic factor in the anterior pituitary gland. In addition, anterior pituitary expression of the long isoform of the prolactin receptor, measured by real-time PCR, increased about 10-fold in transgenic mice expressing the prolactin receptor antagonist, whereas only a modest increase in the S3 short-isoform expression was observed. These results suggest that endogenous prolactin may regulate its own biological actions in the anterior pituitary by inhibiting the expression of the long isoform of the prolactin receptor. In conclusion, our observations suggest that prolactin is involved in the maintenance of physiological cell renewal in the anterior pituitary. Alterations in this physiological role of prolactin could contribute to pituitary tumor development.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; ArgentinaFil: Boutillon, Florence. Universite de Paris V; FranciaFil: Bernadet, Marie. Universite de Paris V; FranciaFil: 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: Goffin, Vincent. Universite de Paris V; FranciaFil: 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; ArgentinaAmerican Physiological Society2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15234Ferraris, Maria Jimena; Boutillon, Florence; Bernadet, Marie; Seilicovich, Adriana; Goffin, Vincent; et al.; Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 302; 3; 1-2012; 356-3640193-18491522-1555enginfo:eu-repo/semantics/altIdentifier/url/http://ajpendo.physiology.org/content/302/3/E356.full.htmlinfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00333.2011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:32Zoai:ri.conicet.gov.ar:11336/15234instacron: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 09:49:33.203CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
title Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
spellingShingle Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
Ferraris, Maria Jimena
Apoptosis
Antiproliferative Effect
∆1-9-G129-Hprl
Long Prolactin Receptor
Short Prolactin Receptor
Prolactin Receptor Isoform
title_short Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
title_full Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
title_fullStr Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
title_full_unstemmed Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
title_sort Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression
dc.creator.none.fl_str_mv Ferraris, Maria Jimena
Boutillon, Florence
Bernadet, Marie
Seilicovich, Adriana
Goffin, Vincent
Pisera, Daniel Alberto
author Ferraris, Maria Jimena
author_facet Ferraris, Maria Jimena
Boutillon, Florence
Bernadet, Marie
Seilicovich, Adriana
Goffin, Vincent
Pisera, Daniel Alberto
author_role author
author2 Boutillon, Florence
Bernadet, Marie
Seilicovich, Adriana
Goffin, Vincent
Pisera, Daniel Alberto
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Antiproliferative Effect
∆1-9-G129-Hprl
Long Prolactin Receptor
Short Prolactin Receptor
Prolactin Receptor Isoform
topic Apoptosis
Antiproliferative Effect
∆1-9-G129-Hprl
Long Prolactin Receptor
Short Prolactin Receptor
Prolactin Receptor Isoform
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Since anterior pituitary expresses prolactin receptors, prolactin secreted by lactotropes could exert autocrine or paracrine actions on anterior pituitary cells. In fact, it has been observed that prolactin inhibits its own expression by lactotropes. Our hypothesis is that prolactin participates in the control of anterior pituitary cell turnover. In the present study, we explored the action of prolactin on proliferation and apoptosis of anterior pituitary cells and its effect on the expression of the prolactin receptor. To determine the activity of endogenous prolactin, we evaluated the effect of the competitive prolactin receptor antagonist Δ1–9-G129R-hPRL in vivo, using transgenic mice that constitutively and systemically express this antagonist. The weight of the pituitary gland and the anterior pituitary proliferation index, determined by BrdU incorporation, were higher in transgenic mice expressing the antagonist than in wild-type littermates. In addition, blockade of prolactin receptor in vitro by Δ1–9-G129R-hPRL increased proliferation and inhibited apoptosis of somatolactotrope GH3 cells and of primary cultures of male rat anterior pituitary cells, including lactotropes. These results suggest that prolactin acts as an autocrine/paracrine antiproliferative and proapoptotic factor in the anterior pituitary gland. In addition, anterior pituitary expression of the long isoform of the prolactin receptor, measured by real-time PCR, increased about 10-fold in transgenic mice expressing the prolactin receptor antagonist, whereas only a modest increase in the S3 short-isoform expression was observed. These results suggest that endogenous prolactin may regulate its own biological actions in the anterior pituitary by inhibiting the expression of the long isoform of the prolactin receptor. In conclusion, our observations suggest that prolactin is involved in the maintenance of physiological cell renewal in the anterior pituitary. Alterations in this physiological role of prolactin could contribute to pituitary tumor development.
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: Boutillon, Florence. Universite de Paris V; Francia
Fil: Bernadet, Marie. Universite de Paris V; Francia
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: Goffin, Vincent. Universite de Paris V; Francia
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 Since anterior pituitary expresses prolactin receptors, prolactin secreted by lactotropes could exert autocrine or paracrine actions on anterior pituitary cells. In fact, it has been observed that prolactin inhibits its own expression by lactotropes. Our hypothesis is that prolactin participates in the control of anterior pituitary cell turnover. In the present study, we explored the action of prolactin on proliferation and apoptosis of anterior pituitary cells and its effect on the expression of the prolactin receptor. To determine the activity of endogenous prolactin, we evaluated the effect of the competitive prolactin receptor antagonist Δ1–9-G129R-hPRL in vivo, using transgenic mice that constitutively and systemically express this antagonist. The weight of the pituitary gland and the anterior pituitary proliferation index, determined by BrdU incorporation, were higher in transgenic mice expressing the antagonist than in wild-type littermates. In addition, blockade of prolactin receptor in vitro by Δ1–9-G129R-hPRL increased proliferation and inhibited apoptosis of somatolactotrope GH3 cells and of primary cultures of male rat anterior pituitary cells, including lactotropes. These results suggest that prolactin acts as an autocrine/paracrine antiproliferative and proapoptotic factor in the anterior pituitary gland. In addition, anterior pituitary expression of the long isoform of the prolactin receptor, measured by real-time PCR, increased about 10-fold in transgenic mice expressing the prolactin receptor antagonist, whereas only a modest increase in the S3 short-isoform expression was observed. These results suggest that endogenous prolactin may regulate its own biological actions in the anterior pituitary by inhibiting the expression of the long isoform of the prolactin receptor. In conclusion, our observations suggest that prolactin is involved in the maintenance of physiological cell renewal in the anterior pituitary. Alterations in this physiological role of prolactin could contribute to pituitary tumor development.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/15234
Ferraris, Maria Jimena; Boutillon, Florence; Bernadet, Marie; Seilicovich, Adriana; Goffin, Vincent; et al.; Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 302; 3; 1-2012; 356-364
0193-1849
1522-1555
url http://hdl.handle.net/11336/15234
identifier_str_mv Ferraris, Maria Jimena; Boutillon, Florence; Bernadet, Marie; Seilicovich, Adriana; Goffin, Vincent; et al.; Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 302; 3; 1-2012; 356-364
0193-1849
1522-1555
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://ajpendo.physiology.org/content/302/3/E356.full.html
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00333.2011
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.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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