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dc.contributor.author
Ferraris, Maria Jimena
dc.contributor.author
Zarate, Sandra Cristina
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Jaita, Gabriela Alejandra
dc.contributor.author
Boutillon, Florencia
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Bernadet, Marie
dc.contributor.author
Auffret, Julien
dc.contributor.author
Seilicovich, Adriana
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Binart, Nadine
dc.contributor.author
Goffin, Vincent
dc.contributor.author
Pisera, Daniel Alberto
dc.date.available
2017-04-11T20:27:28Z
dc.date.issued
2014-05
dc.identifier.citation
Ferraris, Maria Jimena; Zarate, Sandra Cristina; Jaita, Gabriela Alejandra; Boutillon, Florencia; Bernadet, Marie; et al.; Prolactin induces apoptosis of lactotropes in female rodents; Public Library Of Science; Plos One; 9; 5; 5-2014; e97383
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/15175
dc.description.abstract
Anterior pituitary cell turnover occurring during female sexual cycle is a poorly understood process that involves complex regulation of cell proliferation and apoptosis by multiple hormones. In rats, the prolactin (PRL) surge that occurs at proestrus coincides with the highest apoptotic rate. Since anterior pituitary cells express the prolactin receptor (PRLR), we aimed to address the actual role of PRL in the regulation of pituitary cell turnover in cycling females. We showed that acute hyperprolactinemia induced in ovariectomized rats using PRL injection or dopamine antagonist treatment rapidly increased apoptosis and decreased proliferation specifically of PRL producing cells (lactotropes), suggesting a direct regulation of these cell responses by PRL. To demonstrate that apoptosis naturally occurring at proestrus was regulated by transient elevation of endogenous PRL levels, we used PRLR-deficient female mice (PRLRKO) in which PRL signaling is totally abolished. According to our hypothesis, no increase in lactotrope apoptotic rate was observed at proestrus, which likely contributes to pituitary tumorigenesis observed in these animals. To decipher the molecular mechanisms underlying PRL effects, we explored the isoform-specific pattern of PRLR expression in cycling wild type females. This analysis revealed dramatic changes of long versus short PRLR ratio during the estrous cycle, which is particularly relevant since these isoforms exhibit distinct signaling properties. This pattern was markedly altered in a model of chronic PRLR signaling blockade involving transgenic mice expressing a pure PRLR antagonist (TGΔ1–9-G129R-hPRL), providing evidence that PRL regulates the expression of its own receptor in an isoform-specific manner. Taken together, these results demonstrate that i) the PRL surge occurring during proestrus is a major proapoptotic signal for lactotropes, and ii) partial or total deficiencies in PRLR signaling in the anterior pituitary may result in pituitary hyperplasia and eventual prolactinoma development, as observed in TGΔ1–9-G129R-hPRL and PRLRKO mice, respectively.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library Of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Prolactin
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Anterior Pituitary
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Estrous Cycle
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Cell Renewal
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Fisiología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Prolactin induces apoptosis of lactotropes in female rodents
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-04-07T14:28:11Z
dc.journal.volume
9
dc.journal.number
5
dc.journal.pagination
e97383
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Ferraris, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Zarate, Sandra Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Jaita, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Boutillon, Florencia. Universite Paris Sud; Francia
dc.description.fil
Fil: Bernadet, Marie. Universite Paris Descartes; Francia
dc.description.fil
Fil: Auffret, Julien. Universite Paris Sud; Francia
dc.description.fil
Fil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Binart, Nadine. Universite Paris Sud; Francia
dc.description.fil
Fil: Goffin, Vincent. Universite Paris Descartes; Francia
dc.description.fil
Fil: Pisera, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097383
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0097383
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