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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/134879
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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 Técnicas2025-09-03T09:46:46Zoai: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:34982025-09-03 09:46:46.489CONICET 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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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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Fundación Revista Medicina |
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Fundación Revista Medicina |
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