Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice

Dopamine D2 receptor (D2R) knockout (KO) female mice develop chronic hyperprolactinemia and pituitary hyperplasia. Our objective was to study the expression of the mitogen fibroblast growth factor (FGF2) and its receptor, FGFR1, comparatively in pituitaries from KO and wild-type (WT) female mice. We...

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Publicado: 2007
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v293_n5_pE1341_Cristina
http://hdl.handle.net/20.500.12110/paper_01931849_v293_n5_pE1341_Cristina
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spelling paper:paper_01931849_v293_n5_pE1341_Cristina2023-06-08T15:20:04Z Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice Dopaminergic D2 receptor Extracellular signal-regulated kinase phosphorylation Fibroblast growth factor receptor-1 Immunohistochemistry Prolactin dopamine 2 receptor fibroblast growth factor 2 prolactin animal cell animal cell culture animal experiment animal model animal tissue article cell assay cell proliferation cellular distribution chronic disease concentration (parameters) controlled study cytosol DNA synthesis enzyme linked immunosorbent assay enzyme phosphorylation female genotype hyperpituitarism hyperprolactinemia hypophysis function immunofluorescence immunohistochemistry knockout mouse mouse nonhuman priority journal prognosis prolactin release prolactinoma protein localization protein secretion reliability species comparison Western blotting wild type Animals Blotting, Western Cell Growth Processes Enzyme-Linked Immunosorbent Assay Extracellular Signal-Regulated MAP Kinases Female Fibroblast Growth Factor 2 Hyperplasia Immunohistochemistry Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Confocal Microscopy, Fluorescence Phosphorylation Pituitary Gland, Anterior Prolactin Prolactinoma Receptor, Fibroblast Growth Factor, Type 1 Receptors, Dopamine D2 Dopamine D2 receptor (D2R) knockout (KO) female mice develop chronic hyperprolactinemia and pituitary hyperplasia. Our objective was to study the expression of the mitogen fibroblast growth factor (FGF2) and its receptor, FGFR1, comparatively in pituitaries from KO and wild-type (WT) female mice. We also evaluated FGF2 subcellular localization and FGF2 effects on pituitary function. FGF2-induced prolactin release showed a similar response pattern in both genotypes, even though basal and FGF2-stimulated release was higher in KO. FGF2 stimulated pituitary cellular proliferation (MTS assay and [ 3H]thymidine incorporation), with no differences between genotypes. FGF2 concentration (measured by ELISA) in whole pituitaries or cultured cells was lower in KO (P < 0.00001 and 0.00014). Immunofluorescence histochemistry showed less FGF2 in pituitaries from KO females and revealed a distinct FGF2 localization pattern between genotypes, being predominantly nuclear in KO and cytosolic in WT pituitaries. Finally, FGF2 could not be detected in the conditioned media from pituitary cultures of both genotypes. FGFR1 levels (Western blot and immunohistochemistry) were higher in pituitaries of KO. Basal concentration of phosphorylated ERKs was lower in KO cells (P = 0.018). However, when stimulated with FGF2, a significantly higher increment of ERK phosphorylation was evidenced in KO cells (P ≤ 0.02). We conclude that disruption of the D2R caused an overall decrease in pituitary FGF2 levels, with an increased distribution in the nucleus, and increased FGFR1 levels. These results are important in the search for reliable prognostic indicators for patients with pituitary dopamine-resistant prolactinomas, which will make tumor-specific therapy possible. Copyright © 2007 the American Physiological Society. 2007 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v293_n5_pE1341_Cristina http://hdl.handle.net/20.500.12110/paper_01931849_v293_n5_pE1341_Cristina
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Dopaminergic D2 receptor
Extracellular signal-regulated kinase phosphorylation
Fibroblast growth factor receptor-1
Immunohistochemistry
Prolactin
dopamine 2 receptor
fibroblast growth factor 2
prolactin
animal cell
animal cell culture
animal experiment
animal model
animal tissue
article
cell assay
cell proliferation
cellular distribution
chronic disease
concentration (parameters)
controlled study
cytosol
DNA synthesis
enzyme linked immunosorbent assay
enzyme phosphorylation
female
genotype
hyperpituitarism
hyperprolactinemia
hypophysis function
immunofluorescence
immunohistochemistry
knockout mouse
mouse
nonhuman
priority journal
prognosis
prolactin release
prolactinoma
protein localization
protein secretion
reliability
species comparison
Western blotting
wild type
Animals
Blotting, Western
Cell Growth Processes
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases
Female
Fibroblast Growth Factor 2
Hyperplasia
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Microscopy, Fluorescence
Phosphorylation
Pituitary Gland, Anterior
Prolactin
Prolactinoma
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Dopamine D2
spellingShingle Dopaminergic D2 receptor
Extracellular signal-regulated kinase phosphorylation
Fibroblast growth factor receptor-1
Immunohistochemistry
Prolactin
dopamine 2 receptor
fibroblast growth factor 2
prolactin
animal cell
animal cell culture
animal experiment
animal model
animal tissue
article
cell assay
cell proliferation
cellular distribution
chronic disease
concentration (parameters)
controlled study
cytosol
DNA synthesis
enzyme linked immunosorbent assay
enzyme phosphorylation
female
genotype
hyperpituitarism
hyperprolactinemia
hypophysis function
immunofluorescence
immunohistochemistry
knockout mouse
mouse
nonhuman
priority journal
prognosis
prolactin release
prolactinoma
protein localization
protein secretion
reliability
species comparison
Western blotting
wild type
Animals
Blotting, Western
Cell Growth Processes
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases
Female
Fibroblast Growth Factor 2
Hyperplasia
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Microscopy, Fluorescence
Phosphorylation
Pituitary Gland, Anterior
Prolactin
Prolactinoma
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Dopamine D2
Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
topic_facet Dopaminergic D2 receptor
Extracellular signal-regulated kinase phosphorylation
Fibroblast growth factor receptor-1
Immunohistochemistry
Prolactin
dopamine 2 receptor
fibroblast growth factor 2
prolactin
animal cell
animal cell culture
animal experiment
animal model
animal tissue
article
cell assay
cell proliferation
cellular distribution
chronic disease
concentration (parameters)
controlled study
cytosol
DNA synthesis
enzyme linked immunosorbent assay
enzyme phosphorylation
female
genotype
hyperpituitarism
hyperprolactinemia
hypophysis function
immunofluorescence
immunohistochemistry
knockout mouse
mouse
nonhuman
priority journal
prognosis
prolactin release
prolactinoma
protein localization
protein secretion
reliability
species comparison
Western blotting
wild type
Animals
Blotting, Western
Cell Growth Processes
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases
Female
Fibroblast Growth Factor 2
Hyperplasia
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Microscopy, Fluorescence
Phosphorylation
Pituitary Gland, Anterior
Prolactin
Prolactinoma
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Dopamine D2
description Dopamine D2 receptor (D2R) knockout (KO) female mice develop chronic hyperprolactinemia and pituitary hyperplasia. Our objective was to study the expression of the mitogen fibroblast growth factor (FGF2) and its receptor, FGFR1, comparatively in pituitaries from KO and wild-type (WT) female mice. We also evaluated FGF2 subcellular localization and FGF2 effects on pituitary function. FGF2-induced prolactin release showed a similar response pattern in both genotypes, even though basal and FGF2-stimulated release was higher in KO. FGF2 stimulated pituitary cellular proliferation (MTS assay and [ 3H]thymidine incorporation), with no differences between genotypes. FGF2 concentration (measured by ELISA) in whole pituitaries or cultured cells was lower in KO (P < 0.00001 and 0.00014). Immunofluorescence histochemistry showed less FGF2 in pituitaries from KO females and revealed a distinct FGF2 localization pattern between genotypes, being predominantly nuclear in KO and cytosolic in WT pituitaries. Finally, FGF2 could not be detected in the conditioned media from pituitary cultures of both genotypes. FGFR1 levels (Western blot and immunohistochemistry) were higher in pituitaries of KO. Basal concentration of phosphorylated ERKs was lower in KO cells (P = 0.018). However, when stimulated with FGF2, a significantly higher increment of ERK phosphorylation was evidenced in KO cells (P ≤ 0.02). We conclude that disruption of the D2R caused an overall decrease in pituitary FGF2 levels, with an increased distribution in the nucleus, and increased FGFR1 levels. These results are important in the search for reliable prognostic indicators for patients with pituitary dopamine-resistant prolactinomas, which will make tumor-specific therapy possible. Copyright © 2007 the American Physiological Society.
title Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
title_short Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
title_full Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
title_fullStr Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
title_full_unstemmed Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
title_sort fibroblast growth factor-2 in hyperplastic pituitaries of d2r knockout female mice
publishDate 2007
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v293_n5_pE1341_Cristina
http://hdl.handle.net/20.500.12110/paper_01931849_v293_n5_pE1341_Cristina
_version_ 1768545185394851840