Molecular evidence and clinical importance of β-arrestins expression in patients with acromegaly.

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.
(© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)