%0 Journal Article
%A Ibañez-Costa, Alejandro
%A Lopez-Sanchez, Laura M
%A Gahete, Manuel D
%A Rivero-Cortes, Esther
%A Vazquez-Borrego, Mari C
%A Galvez, Maria A
%A de-la-Riva, Andres
%A Venegas-Moreno, Eva
%A Jimenez-Reina, Luis
%A Moreno-Carazo, Alberto
%A Tinahones, Francisco J
%A Maraver-Selfa, Silvia
%A Japon, Miguel A
%A Garcia-Arnes, Juan A
%A Soto-Moreno, Alfonso
%A Webb, Susan M
%A Kineman, Rhonda D
%A Culler, Michael D
%A Castaño, Justo P
%A Luque, Raul M
%T BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas
%D 2017
%U http://hdl.handle.net/10668/2675
%X 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.
%K  Pituitary Neoplasms
%K  Dopamine
%K  Receptors, Somatostatin
%K  Cell Survival 
%K Somatostatin
%K  Adenoma
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