Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats

Autores
Brown, Oscar Alfredo; Canatelli Mallat, Martina; Console de Avegliano, Gloria Miriam; Camihort, Gisela; Luna, Georgina; Spinedi, Eduardo Julio; Goya, Rodolfo Gustavo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibu-lar dopaminergic neuron function in aging female rats. Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats. Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis. Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas. Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats.
Fil: Brown, Oscar Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Console de Avegliano, Gloria Miriam. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Camihort, Gisela. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Luna, Georgina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Materia
ADENOMAS
AGING
GENE THERAPY
HYPOTHALAMUS
IGF-1
PITUITARY
PRL
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:11336/96926
Acceder
id CONICETDig_3de7c57f917669e8deb59aff5885fb8d
oai_identifier_str oai:ri.conicet.gov.ar:11336/96926
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile ratsBrown, Oscar AlfredoCanatelli Mallat, MartinaConsole de Avegliano, Gloria MiriamCamihort, GiselaLuna, GeorginaSpinedi, Eduardo JulioGoya, Rodolfo GustavoADENOMASAGINGGENE THERAPYHYPOTHALAMUSIGF-1PITUITARYPRLhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibu-lar dopaminergic neuron function in aging female rats. Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats. Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis. Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas. Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats.Fil: Brown, Oscar Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Console de Avegliano, Gloria Miriam. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Camihort, Gisela. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Luna, Georgina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaBentham Science Publishers2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96926Brown, Oscar Alfredo; Canatelli Mallat, Martina; Console de Avegliano, Gloria Miriam; Camihort, Gisela; Luna, Georgina; et al.; Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats; Bentham Science Publishers; Current Gene Therapy; 18; 4; 8-2018; 240-2451566-5232CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2174/1566523218666180905170020info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/165158/articleinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:03:26Zoai:ri.conicet.gov.ar:11336/96926instacron: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:34982025-09-10 13:03:26.432CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
title Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
spellingShingle Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
Brown, Oscar Alfredo
ADENOMAS
AGING
GENE THERAPY
HYPOTHALAMUS
IGF-1
PITUITARY
PRL
title_short Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
title_full Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
title_fullStr Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
title_full_unstemmed Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
title_sort Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats
dc.creator.none.fl_str_mv Brown, Oscar Alfredo
Canatelli Mallat, Martina
Console de Avegliano, Gloria Miriam
Camihort, Gisela
Luna, Georgina
Spinedi, Eduardo Julio
Goya, Rodolfo Gustavo
author Brown, Oscar Alfredo
author_facet Brown, Oscar Alfredo
Canatelli Mallat, Martina
Console de Avegliano, Gloria Miriam
Camihort, Gisela
Luna, Georgina
Spinedi, Eduardo Julio
Goya, Rodolfo Gustavo
author_role author
author2 Canatelli Mallat, Martina
Console de Avegliano, Gloria Miriam
Camihort, Gisela
Luna, Georgina
Spinedi, Eduardo Julio
Goya, Rodolfo Gustavo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ADENOMAS
AGING
GENE THERAPY
HYPOTHALAMUS
IGF-1
PITUITARY
PRL
topic ADENOMAS
AGING
GENE THERAPY
HYPOTHALAMUS
IGF-1
PITUITARY
PRL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibu-lar dopaminergic neuron function in aging female rats. Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats. Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis. Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas. Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats.
Fil: Brown, Oscar Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Console de Avegliano, Gloria Miriam. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Camihort, Gisela. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Luna, Georgina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
description Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibu-lar dopaminergic neuron function in aging female rats. Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats. Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis. Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas. Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/96926
Brown, Oscar Alfredo; Canatelli Mallat, Martina; Console de Avegliano, Gloria Miriam; Camihort, Gisela; Luna, Georgina; et al.; Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats; Bentham Science Publishers; Current Gene Therapy; 18; 4; 8-2018; 240-245
1566-5232
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96926
identifier_str_mv Brown, Oscar Alfredo; Canatelli Mallat, Martina; Console de Avegliano, Gloria Miriam; Camihort, Gisela; Luna, Georgina; et al.; Igf-1 gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats; Bentham Science Publishers; Current Gene Therapy; 18; 4; 8-2018; 240-245
1566-5232
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.2174/1566523218666180905170020
info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/165158/article
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.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
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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score 12.993085

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