Artículo

Castillo, V.; Theodoropoulou, M.; Stalla, J.; Gallelli, M.F.; Cabrera-Blatter, M.F.; Haedo, M.R.; Labeur, M.; Schmid, H.A.; Stalla, G.K.; Arzt, E. "Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease" (2011) Neuroendocrinology. 94(2):124-136
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Abstract:

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.

Registro:

Documento: Artículo
Título:Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease
Autor:Castillo, V.; Theodoropoulou, M.; Stalla, J.; Gallelli, M.F.; Cabrera-Blatter, M.F.; Haedo, M.R.; Labeur, M.; Schmid, H.A.; Stalla, G.K.; Arzt, E.
Filiación:Unidad de Endocrinología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina
Max Planck Institute of Psychiatry, Munich, Germany
Laboratorio de Fisiología y Biología Molecular, Depto. de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Aires Ciudad Universitaria, Pabellon II, Buenos Aires 1428, Argentina
Argentine National Research Council, Buenos Aires, Argentina
Novartis Institutes for Biomedical Research, Basel, Switzerland
Palabras clave: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
Año:2011
Volumen:94
Número:2
Página de inicio:124
Página de fin:136
DOI: http://dx.doi.org/10.1159/000327429
Título revista:Neuroendocrinology
Título revista abreviado:Neuroendocrinology
ISSN:00283835
CODEN:NUNDA
CAS:corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; creatinine, 19230-81-0, 60-27-5; hydrocortisone, 50-23-7; pasireotide, 396091-73-9; proopiomelanocortin, 66796-54-1; Adrenocorticotropic Hormone, 9002-60-2; Alanine Transaminase, 2.6.1.2; Alkaline Phosphatase, 3.1.3.1; Aspartate Aminotransferases, 2.6.1.1; Blood Glucose; Cholesterol, 57-88-5; Creatinine, 60-27-5; Hydrocortisone, 50-23-7; Somatostatin, 51110-01-1; Triglycerides; alpha-MSH, 581-05-5; pasireotide
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v94_n2_p124_Castillo

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Citas:

---------- APA ----------
Castillo, V., Theodoropoulou, M., Stalla, J., Gallelli, M.F., Cabrera-Blatter, M.F., Haedo, M.R., Labeur, M.,..., Arzt, E. (2011) . Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease. Neuroendocrinology, 94(2), 124-136.
http://dx.doi.org/10.1159/000327429
---------- CHICAGO ----------
Castillo, V., Theodoropoulou, M., Stalla, J., Gallelli, M.F., Cabrera-Blatter, M.F., Haedo, M.R., et al. "Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease" . Neuroendocrinology 94, no. 2 (2011) : 124-136.
http://dx.doi.org/10.1159/000327429
---------- MLA ----------
Castillo, V., Theodoropoulou, M., Stalla, J., Gallelli, M.F., Cabrera-Blatter, M.F., Haedo, M.R., et al. "Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease" . Neuroendocrinology, vol. 94, no. 2, 2011, pp. 124-136.
http://dx.doi.org/10.1159/000327429
---------- VANCOUVER ----------
Castillo, V., Theodoropoulou, M., Stalla, J., Gallelli, M.F., Cabrera-Blatter, M.F., Haedo, M.R., et al. Effect of SOM230 (Pasireotide) on corticotropic cells: Action in dogs with Cushing's disease. Neuroendocrinology. 2011;94(2):124-136.
http://dx.doi.org/10.1159/000327429