Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease

Autores
Castillo, Victor; Theodoropoulou, Marily; Stalla, Johanna; Gallelli, Maria Florencia; Cabrera Blatter, Maria Fernanda; Haedo, Mariana Raquel; Labeur, Marta; Schmid, Herbert A.; Stalla, Günter K.; Arzt, Eduardo Simon
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
SOM230 (pasireotide) is a multiligand somatostatin (SRIF) analog able to bind to somatostatin receptor (SSTR) subtypes 1, 2, 3 and 5, and trigger antisecretory and antiproliferative signaling cascades. Canines have become in vivo models to test the pharmacological treatment of corticotropinomas because they frequently develop Cushing's disease in a spontaneous manner, due to adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Different levels of expression of SSTR2 and SSTR5 have been shown in both mouse AtT20 cells and canine tumoral corticotropinoma cells. The objective of this study was to evaluate whether SOM230 controls both tumor cell growth and hormone synthesis, therefore controlling the disease. SOM230 was tested in dogs suffering from Cushing's disease (10 animals were treated continuously during 6 months, and another 10 were treated with 3 cycles consisting of 2 months of treatment followed by a 2-month rest period). A significant decrease in ACTH, urinary cortisol creatinine ratio, adenoma size (magnetic nuclear resonance) and improvement of clinical signs were obtained, without side effects. AtT20 cells treated with SOM230 suppressed pro-opiomelanocortin (POMC) promoter activity through SSTR2, via the G i α-subunit, and reduced Nur77/Nurr1 transcriptional activity. We conclude that SOM230, in addition to its well-described antisecretory effects, inhibits, as shown in AtT20 cells, ACTH synthesis at the POMC transcriptional level, an effect mediated mainly through SSTR2, and limits tumor growth. The controlled Cushing's disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing's disease.
Fil: Castillo, Victor. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Johanna. Max Planck Institute of Psychiatry; Alemania
Fil: Gallelli, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabrera Blatter, Maria Fernanda. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Haedo, Mariana Raquel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Labeur, Marta. Max Planck Institute of Psychiatry; Alemania
Fil: Schmid, Herbert A.. Novartis Institutes for Biomedical Research; Suiza
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Corticotropes
Cushing'S Disease
Pituitary Adenoma
Som231
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:11336/68973
Acceder
id CONICETDig_d0489571cf8164a9890d02b21795ea12
oai_identifier_str oai:ri.conicet.gov.ar:11336/68973
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's diseaseCastillo, VictorTheodoropoulou, MarilyStalla, JohannaGallelli, Maria FlorenciaCabrera Blatter, Maria FernandaHaedo, Mariana RaquelLabeur, MartaSchmid, Herbert A.Stalla, Günter K.Arzt, Eduardo SimonCorticotropesCushing'S DiseasePituitary AdenomaSom231SOM230 (pasireotide) is a multiligand somatostatin (SRIF) analog able to bind to somatostatin receptor (SSTR) subtypes 1, 2, 3 and 5, and trigger antisecretory and antiproliferative signaling cascades. Canines have become in vivo models to test the pharmacological treatment of corticotropinomas because they frequently develop Cushing's disease in a spontaneous manner, due to adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Different levels of expression of SSTR2 and SSTR5 have been shown in both mouse AtT20 cells and canine tumoral corticotropinoma cells. The objective of this study was to evaluate whether SOM230 controls both tumor cell growth and hormone synthesis, therefore controlling the disease. SOM230 was tested in dogs suffering from Cushing's disease (10 animals were treated continuously during 6 months, and another 10 were treated with 3 cycles consisting of 2 months of treatment followed by a 2-month rest period). A significant decrease in ACTH, urinary cortisol creatinine ratio, adenoma size (magnetic nuclear resonance) and improvement of clinical signs were obtained, without side effects. AtT20 cells treated with SOM230 suppressed pro-opiomelanocortin (POMC) promoter activity through SSTR2, via the G i α-subunit, and reduced Nur77/Nurr1 transcriptional activity. We conclude that SOM230, in addition to its well-described antisecretory effects, inhibits, as shown in AtT20 cells, ACTH synthesis at the POMC transcriptional level, an effect mediated mainly through SSTR2, and limits tumor growth. The controlled Cushing's disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing's disease.Fil: Castillo, Victor. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; AlemaniaFil: Stalla, Johanna. Max Planck Institute of Psychiatry; AlemaniaFil: Gallelli, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabrera Blatter, Maria Fernanda. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Haedo, Mariana Raquel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Labeur, Marta. Max Planck Institute of Psychiatry; AlemaniaFil: Schmid, Herbert A.. Novartis Institutes for Biomedical Research; SuizaFil: Stalla, Günter K.. Max Planck Institute of Psychiatry; AlemaniaFil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaKarger2011-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/68973Castillo, Victor; Theodoropoulou, Marily; Stalla, Johanna; Gallelli, Maria Florencia; Cabrera Blatter, Maria Fernanda; et al.; Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease; Karger; Neuroendocrinology; 94; 2; 9-2011; 124-1360028-3835CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1159/000327429info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/327429info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:34Zoai:ri.conicet.gov.ar:11336/68973instacron: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 10:04:35.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
title Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
spellingShingle Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
Castillo, Victor
Corticotropes
Cushing'S Disease
Pituitary Adenoma
Som231
title_short Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
title_full Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
title_fullStr Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
title_full_unstemmed Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
title_sort Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
dc.creator.none.fl_str_mv Castillo, Victor
Theodoropoulou, Marily
Stalla, Johanna
Gallelli, Maria Florencia
Cabrera Blatter, Maria Fernanda
Haedo, Mariana Raquel
Labeur, Marta
Schmid, Herbert A.
Stalla, Günter K.
Arzt, Eduardo Simon
author Castillo, Victor
author_facet Castillo, Victor
Theodoropoulou, Marily
Stalla, Johanna
Gallelli, Maria Florencia
Cabrera Blatter, Maria Fernanda
Haedo, Mariana Raquel
Labeur, Marta
Schmid, Herbert A.
Stalla, Günter K.
Arzt, Eduardo Simon
author_role author
author2 Theodoropoulou, Marily
Stalla, Johanna
Gallelli, Maria Florencia
Cabrera Blatter, Maria Fernanda
Haedo, Mariana Raquel
Labeur, Marta
Schmid, Herbert A.
Stalla, Günter K.
Arzt, Eduardo Simon
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Corticotropes
Cushing'S Disease
Pituitary Adenoma
Som231
topic Corticotropes
Cushing'S Disease
Pituitary Adenoma
Som231
dc.description.none.fl_txt_mv SOM230 (pasireotide) is a multiligand somatostatin (SRIF) analog able to bind to somatostatin receptor (SSTR) subtypes 1, 2, 3 and 5, and trigger antisecretory and antiproliferative signaling cascades. Canines have become in vivo models to test the pharmacological treatment of corticotropinomas because they frequently develop Cushing's disease in a spontaneous manner, due to adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Different levels of expression of SSTR2 and SSTR5 have been shown in both mouse AtT20 cells and canine tumoral corticotropinoma cells. The objective of this study was to evaluate whether SOM230 controls both tumor cell growth and hormone synthesis, therefore controlling the disease. SOM230 was tested in dogs suffering from Cushing's disease (10 animals were treated continuously during 6 months, and another 10 were treated with 3 cycles consisting of 2 months of treatment followed by a 2-month rest period). A significant decrease in ACTH, urinary cortisol creatinine ratio, adenoma size (magnetic nuclear resonance) and improvement of clinical signs were obtained, without side effects. AtT20 cells treated with SOM230 suppressed pro-opiomelanocortin (POMC) promoter activity through SSTR2, via the G i α-subunit, and reduced Nur77/Nurr1 transcriptional activity. We conclude that SOM230, in addition to its well-described antisecretory effects, inhibits, as shown in AtT20 cells, ACTH synthesis at the POMC transcriptional level, an effect mediated mainly through SSTR2, and limits tumor growth. The controlled Cushing's disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing's disease.
Fil: Castillo, Victor. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Johanna. Max Planck Institute of Psychiatry; Alemania
Fil: Gallelli, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabrera Blatter, Maria Fernanda. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Haedo, Mariana Raquel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Labeur, Marta. Max Planck Institute of Psychiatry; Alemania
Fil: Schmid, Herbert A.. Novartis Institutes for Biomedical Research; Suiza
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description SOM230 (pasireotide) is a multiligand somatostatin (SRIF) analog able to bind to somatostatin receptor (SSTR) subtypes 1, 2, 3 and 5, and trigger antisecretory and antiproliferative signaling cascades. Canines have become in vivo models to test the pharmacological treatment of corticotropinomas because they frequently develop Cushing's disease in a spontaneous manner, due to adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Different levels of expression of SSTR2 and SSTR5 have been shown in both mouse AtT20 cells and canine tumoral corticotropinoma cells. The objective of this study was to evaluate whether SOM230 controls both tumor cell growth and hormone synthesis, therefore controlling the disease. SOM230 was tested in dogs suffering from Cushing's disease (10 animals were treated continuously during 6 months, and another 10 were treated with 3 cycles consisting of 2 months of treatment followed by a 2-month rest period). A significant decrease in ACTH, urinary cortisol creatinine ratio, adenoma size (magnetic nuclear resonance) and improvement of clinical signs were obtained, without side effects. AtT20 cells treated with SOM230 suppressed pro-opiomelanocortin (POMC) promoter activity through SSTR2, via the G i α-subunit, and reduced Nur77/Nurr1 transcriptional activity. We conclude that SOM230, in addition to its well-described antisecretory effects, inhibits, as shown in AtT20 cells, ACTH synthesis at the POMC transcriptional level, an effect mediated mainly through SSTR2, and limits tumor growth. The controlled Cushing's disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing's disease.
publishDate 2011
dc.date.none.fl_str_mv 2011-09
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/11336/68973
Castillo, Victor; Theodoropoulou, Marily; Stalla, Johanna; Gallelli, Maria Florencia; Cabrera Blatter, Maria Fernanda; et al.; Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease; Karger; Neuroendocrinology; 94; 2; 9-2011; 124-136
0028-3835
CONICET Digital
CONICET
url http://hdl.handle.net/11336/68973
identifier_str_mv Castillo, Victor; Theodoropoulou, Marily; Stalla, Johanna; Gallelli, Maria Florencia; Cabrera Blatter, Maria Fernanda; et al.; Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease; Karger; Neuroendocrinology; 94; 2; 9-2011; 124-136
0028-3835
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1159/000327429
info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/327429
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
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
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 13.13397

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