RT Journal Article
T1 BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas
A1 Ibañez-Costa, Alejandro
A1 Lopez-Sanchez, Laura M
A1 Gahete, Manuel D
A1 Rivero-Cortes, Esther
A1 Vazquez-Borrego, Mari C
A1 Galvez, Maria A
A1 de-la-Riva, Andres
A1 Venegas-Moreno, Eva
A1 Jimenez-Reina, Luis
A1 Moreno-Carazo, Alberto
A1 Tinahones, Francisco J
A1 Maraver-Selfa, Silvia
A1 Japon, Miguel A
A1 Garcia-Arnes, Juan A
A1 Soto-Moreno, Alfonso
A1 Webb, Susan M
A1 Kineman, Rhonda D
A1 Culler, Michael D
A1 Castaño, Justo P
A1 Luque, Raul M
K1  Pituitary Neoplasms
K1  Dopamine
K1  Receptors, Somatostatin
K1  Cell Survival 
K1 Somatostatin
K1  Adenoma
AB Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 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/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.
PB Nature Publishing Group
YR 2017
FD 2017-02-09
LK http://hdl.handle.net/10668/2675
UL http://hdl.handle.net/10668/2675
LA en
NO Ibáñez-Costa A, López-Sánchez LM, Gahete MD, Rivero-Cortés E, Vázquez-Borrego MC, Gálvez MA, et al. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas. Sci Rep. 2017; Feb 9;7:42002
NO This work has been funded by the following grants: Junta de Andalucía (BIO-0139, CTS-1406, PI-639-2012); Ministerio de Economía y Competitividad, Gobierno de España (BFU2013-43282) ; Proyectos de Investigación en Salud FIS, funded by Instituto de Salud Carlos III (PI13-00651, co-funded by ERDF/ESF, “Investing in your future”); Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad ‘CIBERobn’; and Ayuda Merck Serono 2013 (to RML and JPC). Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Merit Award and the National Institutes of Health: R21AG031465 and R01DK088133 (to RDK).
DS RISalud
RD Jun 21, 2025