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 Ibáñez-Costa, Alejandro
A1 López-Sánchez, Laura M
A1 Gahete, Manuel D
A1 Rivero-Cortés, Esther
A1 Vázquez-Borrego, Mari C
A1 Gálvez, María A
A1 de la Riva, Andrés
A1 Venegas-Moreno, Eva
A1 Jiménez-Reina, Luis
A1 Moreno-Carazo, Alberto
A1 Tinahones, Francisco J
A1 Maraver-Selfa, Silvia
A1 Japón, Miguel A
A1 García-Arnés, Juan A
A1 Soto-Moreno, Alfonso
A1 Webb, Susan M
A1 Kineman, Rhonda D
A1 Culler, Michael D
A1 Castaño, Justo P
A1 Luque, Raúl M
K1 Adenoma hipofisario secretor de ACTH
K1 Adenoma
K1 Apoptosis
K1 Supervivencia celular
K1 Dopamina
K1 Humanos
K1 Hormonas hipofisarias
K1 Neoplasias hipofisarias
K1 Primates
K1 Receptores dopaminérgicos
K1 Receptores de somatostatina
K1 Somatostatina
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
DS RISalud
RD Apr 5, 2025