TY - JOUR
T1 - Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly
AU - Gatto, Federico
AU - Biermasz, Nienke R.
AU - Feelders, Richard A.
AU - Kros, Johan M.
AU - Dogan, Fadime
AU - Van Der Lely, Aart Jan
AU - Neggers, Sebastian J.C.M.M.
AU - Lamberts, Steven W.J.
AU - Pereira, Alberto M.
AU - Ferone, Diego
AU - Hofland, Leo J.
N1 - Publisher Copyright:
© 2016 European Society of Endocrinology.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84969972143
U2 - 10.1530/EJE-15-0391
DO - 10.1530/EJE-15-0391
M3 - Article
C2 - 26888629
AN - SCOPUS:84969972143
SN - 0804-4643
VL - 174
SP - 651
EP - 662
JO - European journal of endocrinology
JF - European journal of endocrinology
IS - 5
ER -