Pituitary and neuroendocrinology
Alejandro Ibáñez-Costa 1,2,3,4 , Mari C. Vázquez-Borrego 1,2,3,4 , Paloma Moreno-Moreno 1,5 , Antonio C. Fuentes-Fayos 1,2,3,4 , Ricardo Blázquez-Encinas 1,2,3,4 , Victor García-Vioque 1,2,3,4 , Eva Venegas Moreno 6 , Juan Antonio García Arnés 7 , Aura D. Herrera-Martínez 1,5 , Manuel Gahete Ortiz 1,2,3,4 , Alfonso Soto-Moreno 6 , María Ángeles Gálvez-Moreno 1,5 , Raul M. Luque 1,2,3,4 & Justo P. Castaño 1,2,3,4
1Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; 2Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; 3CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; 4Reina Sofia University Hospital, Córdoba, Spain; 4Endocrinology and Nutrition Service, Reina Sofia University Hospital, Córdoba, Spain; 6Metabolism and Nutrition Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain; 7Carlos Haya University Hospital, Málaga, Spain
Background: Cushing’s disease is the result of prolonged and excessive exposure to cortisol caused by a pituitary tumor. Treatment with somatostatin analogs (SSA), which can reduce hormone secretion and tumor growth in other pituitary tumors (e.g., somatotropinomas), is usually ineffective in corticotropinomas. Previous studies indicated that presence of the truncated SST5TMD4 receptor variant is associated with a lack of response to SSA in acromegaly; but, its presence and functional role in corticotropinomas is still unknown.
Objectives: The aim of this study is to gain further insight on the molecular and functional role of somatostatin receptors (SSTs) in corticotropinoma cells.
Methods: Thus, expression levels of SSTs were measured in 30 corticotropinomas and 8 normal pituitary samples. Functional assays were performed in corticotropinoma primary cell cultures.
Results: In general, we observed a differential expression of SSTs in corticotropinomas compared to normal pituitary samples. A deeper analysis revealed the existence of two corticotropinomas subpopulations that differed in the expression of the receptors. The named ‘high’ population expresses all SSTs, presenting a higher expression SST5TMD4, while the ‘low’ subpopulation, displayed lower SST1/SST2/SST3 levels. Functional studies in primary cultures revealed that both subpopulations differentially respond to in vitro treatment with SSA, octreotide and pasireotide. Finally, SST5TMD4 overexpression increased cell viability.
Conclusions: Our data indicate that there could be two subpopulations of corticotropic tumors, which could confer differential responsiveness to SSA. Furthermore, the presence of SST5TMD4 may be associated with a higher rate of cell proliferation in corticotropinomas. Consequently, a detailed expression profile of all the SSTs in corticotropinomas, especially SST5 variants, could assist the prediction of response to SSA in patients with Cushing’s disease.
Volume 75
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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