Molecular evidence and clinical importance of β‐arrestins expression in patients with acromegaly |
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| Authors: | Maria Caroline Alves Coelho Marina Lipkin Vasquez Luiz Eduardo Wildemberg Mari C. Vázquez‐Borrego Luciana Bitana Aline Helen da Silva Camacho Débora Silva Liana Lumi Ogino Nina Ventura Leila Chimelli Raul M. Luque Leandro Kasuki Mônica R. Gadelha |
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| Affiliation: | 1. Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;2. Endocrine Division, Hospital Universitário Pedro Ernesto, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil;3. Endocrine Division, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, Brazil;4. Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil;5. Neuroendocrinology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil;6. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain;7. Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, Córdoba, Spain;8. Reina Sofia University Hospital, Córdoba, Spain;9. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain;10. Neuropathology Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil;11. Pathology Division, Instituto Nacional do Cancer, Rio de janeiro, Brazil;12. Radiology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil;13. Endocrine Division, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil |
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| Abstract: | β‐arrestins seem to have a role in endocytosis and desensitization of somatostatin receptor subtype 2 (sst2) and could be associated with the responsiveness to somatostatin receptor ligands (SRL) in patients with acromegaly. To investigate the in vivo correlation between β‐arrestins 1 and 2 with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the association of β‐arrestins with response to first‐generation SRL and invasiveness in somatotropinomas. β‐arrestins 1 and 2, sst2, sst5 and D2 mRNA expressions were evaluated by quantitative real‐time RT‐PCR on tumoral tissue of 96 patients. Moreover, sst2 and sst5 protein expressions were also evaluated in 40 somatotropinomas by immunohistochemistry. Response to SRL, defined as GH <1 μg/l and normal IGF‐I levels, was assessed in 40 patients. The Knosp‐Steiner criteria were used to define invasiveness. Median β‐arrestin 1, β‐arrestin 2, sst2, sst5 and D2 mRNA copy numbers were 478; 9375; 731; 156 ; and 3989, respectively. There was a positive correlation between β‐arrestins 1 and 2 (R = 0.444, P < 0.001). However, no correlation between β‐arrestins and sst2, sst5 (mRNA and protein levels) or D2 was found. No association was found between β‐arrestins expression and SRL responsiveness or tumour invasiveness. Although previous data suggest a putative correlation between β‐arrestins and sst2, our data clearly indicated that no association existed between β‐arrestins and sst2, sst5 or D2 expression, nor with response to SRL or tumour invasiveness. Therefore, further studies are required to clarify whether β‐arrestins have a role in the response to treatment with SRL in acromegaly. |
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| Keywords: | acromegaly β ‐arrestins somatostatin receptors dopamine receptor somatostatin receptor ligands |
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