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BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

ABSTRACT: 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 (Ca2+ 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 Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ 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.

SUBMITTER: Ibanez-Costa A

PROVIDER: S-EPMC5299479 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other

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BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

Ibáñez-Costa Alejandro A López-Sánchez Laura M LM Gahete Manuel D MD Rivero-Cortés Esther E Vázquez-Borrego Mari C MC Gálvez María A MA de la Riva Andrés A Venegas-Moreno Eva E Jiménez-Reina Luis L Moreno-Carazo Alberto A Tinahones Francisco J FJ Maraver-Selfa Silvia S Japón Miguel A MA García-Arnés Juan A JA Soto-Moreno Alfonso A Webb Susan M SM Kineman Rhonda D RD Culler Michael D MD Castaño Justo P JP Luque Raúl M RM

Scientific reports 20170209

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D<sub>2</sub> 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<sup>2+</sup> signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), ...[more]

PMID: 28181484

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Dataset Information

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

Publications

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

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