Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. Issue 5 (May 2016)

• Record Type: Journal Article
• Authors: Gatto, Federico; Biermasz, Nienke R; Feelders, Richard A; Kros, Johan M; Dogan, Fadime; van der Lely, Aart-Jan; Neggers, Sebastian J C M M; Lamberts, Steven W J; Pereira, Alberto M; Ferone, Diego; Hofland, Leo J
• Is Part Of: European journal of endocrinology. Volume 174:Issue 5(2016)
• Page Start: 651
• Page End: 662
• Publication Date: 2016-05
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-15-0391
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract: Objective: The high expression of somatostatin receptor subtype 2 (SSTR2 also known as sst2 ) usually present in growth hormone (GH)-secreting adenomas is the rationale for therapy with somatostatin analogs (SSAs) in acromegaly. Although SSTR2 expression is a good predictor for biochemical response to SSA treatment, we still face tumors resistant to SSAs despite high SSTR2 expression. Recently, beta-arrestins (β-arrestins) have been highlighted as key players in the regulation of SSTR2 function. Design: To investigate whether β-arrestins might be useful predictors of responsiveness to long-term SSA treatment in acromegaly, we retrospectively evaluated 35 patients with acromegaly who underwent adenomectomy in two referral centers in The Netherlands. Methods: β-arrestin mRNA levels were evaluated in adenoma samples, together with SSTR2 (and SSTR5) mRNA and protein expression. Biochemical response to long-term SSA treatment (median 12 months) was assessed in 32 patients. Results: β-arrestin 1 and 2 mRNA was significantly lower in adenoma tissues from patients who achieved insulin-like growth factor 1 normalization ( P = 0.024 and P = 0.047) and complete biochemical control ( P = 0.047 and P = 0.039). The SSTR2 mRNA was higher in SSA responder patients compared with the resistant ones ( P = 0.026). This difference was more evident when analyzing the SSTR2/β-arrestin 1 and SSTR2/β-arrestin 2 ratio ( P = 0.011 and P = 0.010). β-arrestin 1 and 2 expression showed a significant trend of higher median values from full responders, partial responders to resistant patients ( P = 0.045 and P = 0.021, respectively). Interestingly, SSTR2 protein expression showed a strong inverse correlation with both β-arrestin 1 and 2 mRNA ( ρ = –0.69, P = 0.0011 and ρ = –0.67, P = 0.0016). Conclusions: Low β-arrestin expression and high SSTR2/β-arrestin ratio correlate with the responsiveness to long-term treatment with SSAs in patients with acromegaly.