Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas

Autores
Camilletti, María Andrea; Abeledo Machado, Alejandra Inés; Faraoni, Erika Yanil; de Fino, Fernanda Teresa; Marcial López, Carla Agustina; Rulli, Susana Beatriz; Ferraris, Jimena; Pisera, Daniel Alberto; Diaz, Graciela Susana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Membrane progesterone receptors (mPRs) are known to mediate rapid non-genomic progesterone (P4) effects in different cell types. We recently demonstrated that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs and mPRα/β activation leads to a decrease in prolactin (PRL) secretion. The role of P4 in prolactinoma development remains unclear. In the present work, pituitary expression of mPRs was studied in a well-known model of prolactinoma, transgenic D2 dopamine receptor-deficient mice (Drd2 KO). Expression of mPRs and the classical P4 receptor (nPR) was found significantly decreased in female Drd2 KO pituitaries compared to their WT counterparts. However, the relative proportion of mPRα and mPRβ was increased (about 60% of total pituitary PRs) in tumoral pituitaries. This elevated proportion of mPR to total PR was also observed in other two animal models of prolactinoma. We also found gender differences: male pituitaries express higher levels of mPRs than females, without genotype differences. Males do not develop prolactinoma, even in the absence of dopaminergic inhibition. Finally, as P4 also regulates PRL secretion indirectly by acting on dopaminergic neurons, we studied mPR expression in hypothalamus. We found that the hypothalamus has high expression of mPRs, representing about 80% of total PRs, without genotype or gender differences. Interestingly, the mPR agonist increased dopamine release in hypothalamic explants. Taken together these findings suggest mPRα/β activation could represent a potential tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs.
Fil: Camilletti, María Andrea. 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: Abeledo Machado, Alejandra Inés. 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: Faraoni, Erika Yanil. 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: de Fino, Fernanda Teresa. 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: Marcial López, Carla Agustina. 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: Rulli, Susana Beatriz. 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: Ferraris, Jimena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Fil: Pisera, Daniel Alberto. 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: Diaz, Graciela Susana. 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
LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Virología
Sociedad Argentina de Nanomedicinas
Materia
PROGESTRONE RECEPTORS
PROLACTINOMAS
PITUITARY
THERAPIES
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:11336/249786
Acceder
id CONICETDig_485517798f03aa4769194f1f58201dc3
oai_identifier_str oai:ri.conicet.gov.ar:11336/249786
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomasCamilletti, María AndreaAbeledo Machado, Alejandra InésFaraoni, Erika Yanilde Fino, Fernanda TeresaMarcial López, Carla AgustinaRulli, Susana BeatrizFerraris, JimenaPisera, Daniel AlbertoDiaz, Graciela SusanaPROGESTRONE RECEPTORSPROLACTINOMASPITUITARYTHERAPIEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Membrane progesterone receptors (mPRs) are known to mediate rapid non-genomic progesterone (P4) effects in different cell types. We recently demonstrated that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs and mPRα/β activation leads to a decrease in prolactin (PRL) secretion. The role of P4 in prolactinoma development remains unclear. In the present work, pituitary expression of mPRs was studied in a well-known model of prolactinoma, transgenic D2 dopamine receptor-deficient mice (Drd2 KO). Expression of mPRs and the classical P4 receptor (nPR) was found significantly decreased in female Drd2 KO pituitaries compared to their WT counterparts. However, the relative proportion of mPRα and mPRβ was increased (about 60% of total pituitary PRs) in tumoral pituitaries. This elevated proportion of mPR to total PR was also observed in other two animal models of prolactinoma. We also found gender differences: male pituitaries express higher levels of mPRs than females, without genotype differences. Males do not develop prolactinoma, even in the absence of dopaminergic inhibition. Finally, as P4 also regulates PRL secretion indirectly by acting on dopaminergic neurons, we studied mPR expression in hypothalamus. We found that the hypothalamus has high expression of mPRs, representing about 80% of total PRs, without genotype or gender differences. Interestingly, the mPR agonist increased dopamine release in hypothalamic explants. Taken together these findings suggest mPRα/β activation could represent a potential tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs.Fil: Camilletti, María Andrea. 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: Abeledo Machado, Alejandra Inés. 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: Faraoni, Erika Yanil. 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: de Fino, Fernanda Teresa. 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: Marcial López, Carla Agustina. 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: Rulli, Susana Beatriz. 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: Ferraris, Jimena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; ArgentinaFil: Pisera, Daniel Alberto. 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: Diaz, Graciela Susana. 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; ArgentinaLXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaSociedad Argentina de Investigación ClínicaSociedad Argentina de VirologíaSociedad Argentina de NanomedicinasFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/249786Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2018; 1-21669-9106CONICET DigitalCONICETengSociedad Argentina de Nanomedicinasinfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/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 Técnicas2025-10-22T12:04:33Zoai:ri.conicet.gov.ar:11336/249786instacron: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:34982025-10-22 12:04:33.606CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
title Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
spellingShingle Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
Camilletti, María Andrea
PROGESTRONE RECEPTORS
PROLACTINOMAS
PITUITARY
THERAPIES
title_short Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
title_full Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
title_fullStr Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
title_full_unstemmed Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
title_sort Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas
dc.creator.none.fl_str_mv Camilletti, María Andrea
Abeledo Machado, Alejandra Inés
Faraoni, Erika Yanil
de Fino, Fernanda Teresa
Marcial López, Carla Agustina
Rulli, Susana Beatriz
Ferraris, Jimena
Pisera, Daniel Alberto
Diaz, Graciela Susana
author Camilletti, María Andrea
author_facet Camilletti, María Andrea
Abeledo Machado, Alejandra Inés
Faraoni, Erika Yanil
de Fino, Fernanda Teresa
Marcial López, Carla Agustina
Rulli, Susana Beatriz
Ferraris, Jimena
Pisera, Daniel Alberto
Diaz, Graciela Susana
author_role author
author2 Abeledo Machado, Alejandra Inés
Faraoni, Erika Yanil
de Fino, Fernanda Teresa
Marcial López, Carla Agustina
Rulli, Susana Beatriz
Ferraris, Jimena
Pisera, Daniel Alberto
Diaz, Graciela Susana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROGESTRONE RECEPTORS
PROLACTINOMAS
PITUITARY
THERAPIES
topic PROGESTRONE RECEPTORS
PROLACTINOMAS
PITUITARY
THERAPIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Membrane progesterone receptors (mPRs) are known to mediate rapid non-genomic progesterone (P4) effects in different cell types. We recently demonstrated that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs and mPRα/β activation leads to a decrease in prolactin (PRL) secretion. The role of P4 in prolactinoma development remains unclear. In the present work, pituitary expression of mPRs was studied in a well-known model of prolactinoma, transgenic D2 dopamine receptor-deficient mice (Drd2 KO). Expression of mPRs and the classical P4 receptor (nPR) was found significantly decreased in female Drd2 KO pituitaries compared to their WT counterparts. However, the relative proportion of mPRα and mPRβ was increased (about 60% of total pituitary PRs) in tumoral pituitaries. This elevated proportion of mPR to total PR was also observed in other two animal models of prolactinoma. We also found gender differences: male pituitaries express higher levels of mPRs than females, without genotype differences. Males do not develop prolactinoma, even in the absence of dopaminergic inhibition. Finally, as P4 also regulates PRL secretion indirectly by acting on dopaminergic neurons, we studied mPR expression in hypothalamus. We found that the hypothalamus has high expression of mPRs, representing about 80% of total PRs, without genotype or gender differences. Interestingly, the mPR agonist increased dopamine release in hypothalamic explants. Taken together these findings suggest mPRα/β activation could represent a potential tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs.
Fil: Camilletti, María Andrea. 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: Abeledo Machado, Alejandra Inés. 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: Faraoni, Erika Yanil. 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: de Fino, Fernanda Teresa. 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: Marcial López, Carla Agustina. 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: Rulli, Susana Beatriz. 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: Ferraris, Jimena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Fil: Pisera, Daniel Alberto. 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: Diaz, Graciela Susana. 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
LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Virología
Sociedad Argentina de Nanomedicinas
description Membrane progesterone receptors (mPRs) are known to mediate rapid non-genomic progesterone (P4) effects in different cell types. We recently demonstrated that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs and mPRα/β activation leads to a decrease in prolactin (PRL) secretion. The role of P4 in prolactinoma development remains unclear. In the present work, pituitary expression of mPRs was studied in a well-known model of prolactinoma, transgenic D2 dopamine receptor-deficient mice (Drd2 KO). Expression of mPRs and the classical P4 receptor (nPR) was found significantly decreased in female Drd2 KO pituitaries compared to their WT counterparts. However, the relative proportion of mPRα and mPRβ was increased (about 60% of total pituitary PRs) in tumoral pituitaries. This elevated proportion of mPR to total PR was also observed in other two animal models of prolactinoma. We also found gender differences: male pituitaries express higher levels of mPRs than females, without genotype differences. Males do not develop prolactinoma, even in the absence of dopaminergic inhibition. Finally, as P4 also regulates PRL secretion indirectly by acting on dopaminergic neurons, we studied mPR expression in hypothalamus. We found that the hypothalamus has high expression of mPRs, representing about 80% of total PRs, without genotype or gender differences. Interestingly, the mPR agonist increased dopamine release in hypothalamic explants. Taken together these findings suggest mPRα/β activation could represent a potential tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
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/11336/249786
Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2018; 1-2
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/249786
identifier_str_mv Activation of membrane progesterone receptors (mPRs) represents a novel tool for prolactin inhibition in animal models of prolactinomas; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2018; 1-2
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Sociedad Argentina de Nanomedicinas
info:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/
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.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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