Ibáñez-Costa, AlejandroLópez-Sánchez, Laura MGahete, Manuel DRivero-Cortés, EstherVázquez-Borrego, Mari CGálvez, María Ade la Riva, AndrésVenegas-Moreno, EvaJiménez-Reina, LuisMoreno-Carazo, AlbertoTinahones, Francisco JMaraver-Selfa, SilviaJapón, Miguel AGarcía-Arnés, Juan ASoto-Moreno, AlfonsoWebb, Susan MKineman, Rhonda DCuller, Michael DCastaño, Justo PLuque, Raúl M2017-05-262017-05-262017-02-09Ibáñez-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;7:42002http://hdl.handle.net/10668/2675Chimeric 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.enAdenoma hipofisario secretor de ACTHAdenomaApoptosisSupervivencia celularDopaminaHumanosHormonas hipofisariasNeoplasias hipofisariasPrimatesReceptores dopaminérgicosReceptores de somatostatinaSomatostatinaMedical Subject Headings::Diseases::Endocrine System Diseases::Endocrine Gland Neoplasms::Pituitary Neoplasms::ACTH-Secreting Pituitary AdenomaMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::AdenomaMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell SurvivalMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Catecholamines::DopamineMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary HormonesMedical Subject Headings::Diseases::Endocrine System Diseases::Pituitary Diseases::Pituitary NeoplasmsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::PrimatesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Neurotransmitter::Receptors, Biogenic Amine::Receptors, Catecholamine::Receptors, DopamineMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Neurotransmitter::Receptors, Neuropeptide::Receptors, SomatostatinMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Hypothalamic Hormones::Pituitary Hormone Release Inhibiting Hormones::Somatostatinresearch article28181484open access10.1038/srep420022045-2322PMC5299479