Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly

Federico Gatto, Nienke R. Biermasz, Richard A. Feelders, Johan M. Kros, Fadime Dogan, Aart Jan Van Der Lely, Sebastian J.C.M.M. Neggers, Steven W.J. Lamberts, Alberto M. Pereira, Diego Ferone, Leo J. Hofland

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42 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)651-662
Aantal pagina's12
TijdschriftEuropean Journal of Endocrinology
Volume174
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 1 mei 2016
Extern gepubliceerdJa

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