The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol

Autores
Abeledo Machado, Alejandra Inés; Camilletti, María Andrea; Peña, Milagros; Diaz, Graciela Susana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
TGFβ1 is a potent inhibitor of lactotroph cell proliferation and prolactin (PRL) secretion and Tissue Kallikrein (KLK1) was described as an important activator of latent TGFβ1 in vivo. The Kallikrein-Kinin System (KKS) is complex; kininogens are cleaved by KLK1, releasing kinins, which exert their effect throw its receptors B1R and B2R. Whereas B2R is constitutively expressed, B1R is inducible in pathological conditions. We have previously found that the pituitary expression of most components of the KKS, as well as local TGFβ1 activity, is reduced in prolactinomas. Then we postulate that the recovery of pituitary KKS, could improve local TGFβ1 activity counteracting prolactinoma development. To this end, we first deepen the study of the pituitary KKS regulation by dopamine and estradiol and the pituitary cell types expressing kinins receptors. Female mice lacking the dopamine receptor type 2 (Drd2KO, prolactinoma) vs WT counterpart were used. 1- Double immunofluorescences were performed to assay B2R expression in different pituitary cell-types in WT females. We found that lactotrophs, somatotrophs and gonadotrophs express B2R. 2- Adult females were injected with E2 valerate (0.2mg/kg, sc), cabergoline (DA agonist, 2mg/Kg, ip), sulpiride (DA antagonist, 5mg/kg, ip) or vehicle (castor oil or saline) and were sacrificed after 3 hours. Pituitary expression of KKS components was evaluated by RTqPCR. We found that E2 exerts a negative regulation of Klk1, b2r and b1r expression in WT females, but this control is lost in Drd2KO. On the contrary, DA exerts a positive regulation of Klk1 expression but negatively regulates b2r expression in WT females. We conclude that the positive DA-regulation exercised on the pituitary KLK1 expression is lost in the Drd2KO pituitary, reducing KLK1 local activity, reducing TGFβ1 activation, and contributing to prolactinoma development. The improvement of pituitary KKS activity could represent a novel treatment for resistant prolactinomas.
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: 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional; Argentina
Fil: Peña, Milagros. 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
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del PLata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
KALLIKREIN
PITUITARY
TGFb
PROLACTIN
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:11336/134879
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/134879
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiolAbeledo Machado, Alejandra InésCamilletti, María AndreaPeña, MilagrosDiaz, Graciela SusanaKALLIKREINPITUITARYTGFbPROLACTINhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3TGFβ1 is a potent inhibitor of lactotroph cell proliferation and prolactin (PRL) secretion and Tissue Kallikrein (KLK1) was described as an important activator of latent TGFβ1 in vivo. The Kallikrein-Kinin System (KKS) is complex; kininogens are cleaved by KLK1, releasing kinins, which exert their effect throw its receptors B1R and B2R. Whereas B2R is constitutively expressed, B1R is inducible in pathological conditions. We have previously found that the pituitary expression of most components of the KKS, as well as local TGFβ1 activity, is reduced in prolactinomas. Then we postulate that the recovery of pituitary KKS, could improve local TGFβ1 activity counteracting prolactinoma development. To this end, we first deepen the study of the pituitary KKS regulation by dopamine and estradiol and the pituitary cell types expressing kinins receptors. Female mice lacking the dopamine receptor type 2 (Drd2KO, prolactinoma) vs WT counterpart were used. 1- Double immunofluorescences were performed to assay B2R expression in different pituitary cell-types in WT females. We found that lactotrophs, somatotrophs and gonadotrophs express B2R. 2- Adult females were injected with E2 valerate (0.2mg/kg, sc), cabergoline (DA agonist, 2mg/Kg, ip), sulpiride (DA antagonist, 5mg/kg, ip) or vehicle (castor oil or saline) and were sacrificed after 3 hours. Pituitary expression of KKS components was evaluated by RTqPCR. We found that E2 exerts a negative regulation of Klk1, b2r and b1r expression in WT females, but this control is lost in Drd2KO. On the contrary, DA exerts a positive regulation of Klk1 expression but negatively regulates b2r expression in WT females. We conclude that the positive DA-regulation exercised on the pituitary KLK1 expression is lost in the Drd2KO pituitary, reducing KLK1 local activity, reducing TGFβ1 activation, and contributing to prolactinoma development. The improvement of pituitary KKS activity could represent a novel treatment for resistant prolactinomas.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; ArgentinaFil: 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional; ArgentinaFil: Peña, Milagros. 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; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PLataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/134879The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del PLata; Argentina; 2019; 216-2170025-7680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:12Zoai:ri.conicet.gov.ar:11336/134879instacron: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:34982025-09-29 09:38:13.106CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
title The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
spellingShingle The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
Abeledo Machado, Alejandra Inés
KALLIKREIN
PITUITARY
TGFb
PROLACTIN
title_short The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
title_full The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
title_fullStr The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
title_full_unstemmed The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
title_sort The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol
dc.creator.none.fl_str_mv Abeledo Machado, Alejandra Inés
Camilletti, María Andrea
Peña, Milagros
Diaz, Graciela Susana
author Abeledo Machado, Alejandra Inés
author_facet Abeledo Machado, Alejandra Inés
Camilletti, María Andrea
Peña, Milagros
Diaz, Graciela Susana
author_role author
author2 Camilletti, María Andrea
Peña, Milagros
Diaz, Graciela Susana
author2_role author
author
author
dc.subject.none.fl_str_mv KALLIKREIN
PITUITARY
TGFb
PROLACTIN
topic KALLIKREIN
PITUITARY
TGFb
PROLACTIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv TGFβ1 is a potent inhibitor of lactotroph cell proliferation and prolactin (PRL) secretion and Tissue Kallikrein (KLK1) was described as an important activator of latent TGFβ1 in vivo. The Kallikrein-Kinin System (KKS) is complex; kininogens are cleaved by KLK1, releasing kinins, which exert their effect throw its receptors B1R and B2R. Whereas B2R is constitutively expressed, B1R is inducible in pathological conditions. We have previously found that the pituitary expression of most components of the KKS, as well as local TGFβ1 activity, is reduced in prolactinomas. Then we postulate that the recovery of pituitary KKS, could improve local TGFβ1 activity counteracting prolactinoma development. To this end, we first deepen the study of the pituitary KKS regulation by dopamine and estradiol and the pituitary cell types expressing kinins receptors. Female mice lacking the dopamine receptor type 2 (Drd2KO, prolactinoma) vs WT counterpart were used. 1- Double immunofluorescences were performed to assay B2R expression in different pituitary cell-types in WT females. We found that lactotrophs, somatotrophs and gonadotrophs express B2R. 2- Adult females were injected with E2 valerate (0.2mg/kg, sc), cabergoline (DA agonist, 2mg/Kg, ip), sulpiride (DA antagonist, 5mg/kg, ip) or vehicle (castor oil or saline) and were sacrificed after 3 hours. Pituitary expression of KKS components was evaluated by RTqPCR. We found that E2 exerts a negative regulation of Klk1, b2r and b1r expression in WT females, but this control is lost in Drd2KO. On the contrary, DA exerts a positive regulation of Klk1 expression but negatively regulates b2r expression in WT females. We conclude that the positive DA-regulation exercised on the pituitary KLK1 expression is lost in the Drd2KO pituitary, reducing KLK1 local activity, reducing TGFβ1 activation, and contributing to prolactinoma development. The improvement of pituitary KKS activity could represent a novel treatment for resistant prolactinomas.
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: 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional; Argentina
Fil: Peña, Milagros. 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
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del PLata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description TGFβ1 is a potent inhibitor of lactotroph cell proliferation and prolactin (PRL) secretion and Tissue Kallikrein (KLK1) was described as an important activator of latent TGFβ1 in vivo. The Kallikrein-Kinin System (KKS) is complex; kininogens are cleaved by KLK1, releasing kinins, which exert their effect throw its receptors B1R and B2R. Whereas B2R is constitutively expressed, B1R is inducible in pathological conditions. We have previously found that the pituitary expression of most components of the KKS, as well as local TGFβ1 activity, is reduced in prolactinomas. Then we postulate that the recovery of pituitary KKS, could improve local TGFβ1 activity counteracting prolactinoma development. To this end, we first deepen the study of the pituitary KKS regulation by dopamine and estradiol and the pituitary cell types expressing kinins receptors. Female mice lacking the dopamine receptor type 2 (Drd2KO, prolactinoma) vs WT counterpart were used. 1- Double immunofluorescences were performed to assay B2R expression in different pituitary cell-types in WT females. We found that lactotrophs, somatotrophs and gonadotrophs express B2R. 2- Adult females were injected with E2 valerate (0.2mg/kg, sc), cabergoline (DA agonist, 2mg/Kg, ip), sulpiride (DA antagonist, 5mg/kg, ip) or vehicle (castor oil or saline) and were sacrificed after 3 hours. Pituitary expression of KKS components was evaluated by RTqPCR. We found that E2 exerts a negative regulation of Klk1, b2r and b1r expression in WT females, but this control is lost in Drd2KO. On the contrary, DA exerts a positive regulation of Klk1 expression but negatively regulates b2r expression in WT females. We conclude that the positive DA-regulation exercised on the pituitary KLK1 expression is lost in the Drd2KO pituitary, reducing KLK1 local activity, reducing TGFβ1 activation, and contributing to prolactinoma development. The improvement of pituitary KKS activity could represent a novel treatment for resistant prolactinomas.
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/11336/134879
The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del PLata; Argentina; 2019; 216-217
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/134879
identifier_str_mv The kallikrein-Kinin System in the pituitary gland is involved in lactotroph function and controlled by dopamine and estradiol; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del PLata; Argentina; 2019; 216-217
0025-7680
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://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdf
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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)
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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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