BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries : molecular mechanisms underlying the differential response in adenomas
Ibáñez-Costa, Alejandro (Campus de Excelencia Internacional Agroalimentario (ceiA3))
López-Sánchez, Laura M. (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Gahete, Manuel D. (Campus de Excelencia Internacional Agroalimentario (ceiA3))
Rivero-Cortés, Esther (Campus de Excelencia Internacional Agroalimentario (ceiA3))
Vázquez-Borrego, Mari C. (Campus de Excelencia Internacional Agroalimentario (ceiA3))
Gálvez, María A. (Service of Endocrinology and Nutrition, IMIBIC)
de la Riva, Andrés (Service of Neurosurgery, HURS)
Venegas-Moreno, Eva (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Jiménez-Reina, Luis (University of Cordoba)
Moreno-Carazo, Alberto (Complejo Hospitalario de Jaén)
Tinahones, Francisco J. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Maraver-Selfa, Silvia (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Japón, Miguel A. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
García-Arnés, Juan A. (Hospital Regional Universitario de Málaga)
Soto-Moreno, Alfonso (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Webb, Susan 1952- (Institut d'Investigació Biomèdica Sant Pau)
Kineman, Rhonda D. (University of Illinois at Chicago)
Culler, Michael D. (IPSEN Bioscience, Cambridge)
Castaño, Justo P. (Campus de Excelencia Internacional Agroalimentario (ceiA3))
Luque, Raúl M. (Campus de Excelencia Internacional Agroalimentario (ceiA3))
Universitat Autònoma de Barcelona

Fecha:	2017
Resumen:	Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca 2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca 2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca 2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca 2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.
Ayudas:	Instituto de Salud Carlos III BFU2013-43282 Instituto de Salud Carlos III PI13-00651
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Scientific reports, Vol. 7 (02 2017) , ISSN 2045-2322

DOI: 10.1038/srep42002
PMID: 28181484

14 p, 1.3 MB

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