ECE2014 Oral Communications Pituitary Basic (5 abstracts)
Differential in vitro response to octreotide and pasireotide in normal and tumoral primary pituitary cell cultures
Alejandro Ibáñez-Costa 1 , Manuel David Gahete 1 , Luis Jiménez-Reina 2 , Esther Rivero-Cortés 1 , Laura María López-Sánchez 1 , María Ángeles Gálvez 3 , Andrés de la Riva 4 , Pedro Benito-López 3 , Eva Venegas-Moreno 5 , Miguel Ángel Japón 6 , Alberto Moreno 7 , Juan Antonio García-Arnés 8 , Silvia Maraver-Selfa 9 , Miguel Ángel Arraez 10 , Alfonso Leal-Cerro 5 , Herbert A. Schmid 11 , Francisco J. Tinahones 9 , Alfonso Soto-Moreno 5 , Justo P. Castaño 1 & Raúl M. Luque 1
1Department of Cell Biology, Physiology and Immunology of University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC); CIBER Fisiopatolog, Córdoba, Spain; 2Department of Morphological Sciences, University of Córdoba, Córdoba, Spain; 3Service of Endocrinology and Nutrition, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain; 4Service of Neurosurgery, Reina Sofía University Hospital, Córdoba, Spain; 5Instituto de Biomedicina de Sevilla, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville and Endocrinology, Metabolism and Nutrition Unit, Virgen, Sevilla, Spain; 6Department of Pathology, Virgen del Rocio University Hospital, Sevilla, Spain; 7Endocrinology and Nutrition Unit, Complejo Hospitalario de Jaén, Jaén, Spain; 8Department of Endocrinology and Nutrition, Carlos Haya Hospital, Málaga, Spain; 9Service of Endocrinology and Nutrition, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain; 10Service of Neurosurgery, Carlos Haya Hospital, Málaga, Spain; 11Novartis Pharmaceuticals, Basel, Switzerland.
Somatostatin analogs (SSA) are a first-line treatment for pituitary adenomas (PA). Indeed, multi-receptor targeting SSA such as octreotide and pasireotide are being successfully used to control hormone secretion and/or tumor growth. Unfortunately, many PA escape from SSA-therapy, which could be related to somatostatin receptor (sst) presence, abundance, availability and/or signaling. In order to better define the molecular/cellular features associated to octreotide and pasireotide responsiveness, we have established a reliable methodology to evaluate, in parallel, the in vitro response to octreotide and pasireotide using primary PA cultures by assessing sst-signaling (free-cytosolic (Ca2+) kinetics) and secretory and proliferative responses. In addition, expression of pituitary hormones and ssts using RT-PCR and, hormonal secretion by immuno-blotting was assessed. A total of 44 samples (16 somatotropinomas, 6 corticotropinomas, 5 prolactinomas, 15 non-functioning PA (NFPA) and 2 normal pituitaries) were evaluated. Octreotide and pasireotide treatment decrease (Ca2+) kinetics in 13/16 and 7/16 somatotropinomas respectively; while both SSA similarly inhibited GH secretion and proliferation. Inhibition of (Ca2+) kinetics in response to octreotide and pasireotide were observed in 2/6 and 4/6 corticotropinomas, although it only occurs in a small proportion of cells, whereas ACTH release was not significantly affected. In prolactinomas, only octreotide inhibited (Ca2+) kinetics. In NFPA, both SSA moderately decreased (Ca2+) kinetics (few responsive PA, with moderate inhibition and small proportion of responsive cells), while surprisingly, both SSA stimulated cell proliferation in a considerable proportion of PA. Finally, octreotide did not alter (Ca2+) kinetics in normal pituitary cultures while, pasireotide exerted a faint inhibitory response. The differential response to octreotide and/or pasireotide could not be explained by significant differences in sst-expression pattern between responsive and non-responsive PA. Altogether, our data indicate the existence of a differential in vitroresponse to octreotide and pasireotide in normal and tumoral primary pituitary cell cultures and therefore, further studies are necessary to unveil the key factors involved in this differential responsiveness to SSA.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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