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

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.

• Authors: 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
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 174 Issue 5 Pg. 651-62 (May 2016) ISSN: 1479-683X [Electronic] England
• PMID: 26888629 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 European Society of Endocrinology.

Chemical References

• ARRB1 protein, human
• ARRB2 protein, human
• Arrestins
• RNA, Messenger
• Receptors, Somatostatin
• SSTR2 protein, human
• beta-Arrestin 1
• beta-Arrestin 2
• beta-Arrestins
• Somatostatin
• somatostatin receptor 5

Topics

• Acromegaly (drug therapy, metabolism)
• Adult
• Aged
• Arrestins (metabolism)
• Female
• Gene Expression
• Humans
• Male
• Middle Aged
• RNA, Messenger
• Receptors, Somatostatin (metabolism)
• Retrospective Studies
• Somatostatin (administration & dosage, analogs & derivatives, pharmacology)
• Treatment Outcome
• Young Adult
• beta-Arrestin 1
• beta-Arrestin 2
• beta-Arrestins