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

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 beca...

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Publicado:	2011
Materias:	Corticotropes Cushing's disease Pituitary adenoma SOM231 corticotropin creatinine hydrocortisone pasireotide proopiomelanocortin somatostatin receptor 2 somatostatin receptor 5 ACTH secreting adenoma ACTH secreting cell animal cell animal experiment animal model article controlled study Cushing disease dog drug mechanism drug receptor binding female hormone synthesis male nonhuman priority journal protein expression tumor growth tumor volume Adrenocorticotropic Hormone Alanine Transaminase Alkaline Phosphatase alpha-MSH Animals Aspartate Aminotransferases Blood Glucose Cell Line, Tumor Cholesterol Corticotrophs Creatinine Dogs Female Hydrocortisone Liver Function Tests Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Somatostatin Triglycerides
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v94_n2_p124_Castillo http://hdl.handle.net/20.500.12110/paper_00283835_v94_n2_p124_Castillo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00283835_v94_n2_p124_Castillo
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spelling	paper:paper_00283835_v94_n2_p124_Castillo2023-06-08T14:55:07Z Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease Corticotropes Cushing's disease Pituitary adenoma SOM231 corticotropin creatinine hydrocortisone pasireotide proopiomelanocortin somatostatin receptor 2 somatostatin receptor 5 ACTH secreting adenoma ACTH secreting cell animal cell animal experiment animal model article controlled study Cushing disease dog drug mechanism drug receptor binding female hormone synthesis male nonhuman priority journal protein expression tumor growth tumor volume Adrenocorticotropic Hormone Alanine Transaminase Alkaline Phosphatase alpha-MSH Animals Aspartate Aminotransferases Blood Glucose Cell Line, Tumor Cholesterol Corticotrophs Creatinine Dogs Female Hydrocortisone Liver Function Tests Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Somatostatin Triglycerides 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. Copyright © 2011 S. Karger AG, Basel. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v94_n2_p124_Castillo http://hdl.handle.net/20.500.12110/paper_00283835_v94_n2_p124_Castillo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Corticotropes Cushing's disease Pituitary adenoma SOM231 corticotropin creatinine hydrocortisone pasireotide proopiomelanocortin somatostatin receptor 2 somatostatin receptor 5 ACTH secreting adenoma ACTH secreting cell animal cell animal experiment animal model article controlled study Cushing disease dog drug mechanism drug receptor binding female hormone synthesis male nonhuman priority journal protein expression tumor growth tumor volume Adrenocorticotropic Hormone Alanine Transaminase Alkaline Phosphatase alpha-MSH Animals Aspartate Aminotransferases Blood Glucose Cell Line, Tumor Cholesterol Corticotrophs Creatinine Dogs Female Hydrocortisone Liver Function Tests Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Somatostatin Triglycerides
spellingShingle	Corticotropes Cushing's disease Pituitary adenoma SOM231 corticotropin creatinine hydrocortisone pasireotide proopiomelanocortin somatostatin receptor 2 somatostatin receptor 5 ACTH secreting adenoma ACTH secreting cell animal cell animal experiment animal model article controlled study Cushing disease dog drug mechanism drug receptor binding female hormone synthesis male nonhuman priority journal protein expression tumor growth tumor volume Adrenocorticotropic Hormone Alanine Transaminase Alkaline Phosphatase alpha-MSH Animals Aspartate Aminotransferases Blood Glucose Cell Line, Tumor Cholesterol Corticotrophs Creatinine Dogs Female Hydrocortisone Liver Function Tests Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Somatostatin Triglycerides Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
topic_facet	Corticotropes Cushing's disease Pituitary adenoma SOM231 corticotropin creatinine hydrocortisone pasireotide proopiomelanocortin somatostatin receptor 2 somatostatin receptor 5 ACTH secreting adenoma ACTH secreting cell animal cell animal experiment animal model article controlled study Cushing disease dog drug mechanism drug receptor binding female hormone synthesis male nonhuman priority journal protein expression tumor growth tumor volume Adrenocorticotropic Hormone Alanine Transaminase Alkaline Phosphatase alpha-MSH Animals Aspartate Aminotransferases Blood Glucose Cell Line, Tumor Cholesterol Corticotrophs Creatinine Dogs Female Hydrocortisone Liver Function Tests Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Somatostatin Triglycerides
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. Copyright © 2011 S. Karger AG, Basel.
title	Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
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
publishDate	2011
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v94_n2_p124_Castillo http://hdl.handle.net/20.500.12110/paper_00283835_v94_n2_p124_Castillo
_version_	1768545916042608640

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

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