β-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: Role in the regulation of response to somatostatin analogue treatment in patients with acromegaly

Federico Gatto, Richard Feelders, Rob Van Der Pas, Johan M. Kros, Fadime Dogan, Peter M. Van Koetsveld, Aart Jan Van Der Lelij, Sebastian J C M M Neggers, Francesco Minuto, Wouter De Herder, Steven W J Lamberts, Diego Ferone, Leo J. Hofland

Research output: Contribution to journalArticle

Abstract

Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK)2 and β-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and β-arrestins expression in different pituitary adenomas and to investigate their potential role in the response to somatostatin analog (SSA) treatment in GH-secreting adenomas (GHomas). We evaluated mRNA expression of multiple SSTRs, GRK2, β-arrestin 1, and β-arrestin 2 in 41 pituitary adenomas (31 GHomas, 6 nonfunctioning [NFPAs], and 4 prolactinomas [PRLomas]). Within the GHomas group, mRNA data were correlated with the in vivo response to an acute octreotide test and with the GH-lowering effect of SSA in cultured primary cells. β-Arrestin 1 expression was low in all 3 adenoma histotypes. However, its expression was significantly lower in GHomas and PRLomas, compared with NFPAs (P <.01). GRK2 expression was higher in PRLomas and NFPAs compared with GHomas (P <.05). In the GHoma group, GRK2 expression was inversely correlated to β-arrestin 1 (P <.05) and positively correlated to β-arrestin 2 (P <.0001). SSA treatment did not affect GRK2 and β-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, β-arrestin 1 was significantly lower (P <.05) in tumors responsive to octreotide treatment in vitro, whereas GRK2 and SSTR subtype 2 were significantly higher (P <.05). Likewise, β-arrestin 1 levels were inversely correlated with the in vivo response to acute octreotide test (P = .001), whereas GRK2 and SSTR subtype 2 expression were positively correlated (P <.05). In conclusion, for the first time, we characterized GRK2, β-arrestin 1, and β-arrestin 2 expression in a representative number of pituitary adenomas. β-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.

Original languageEnglish
Pages (from-to)4715-4725
Number of pages11
JournalEndocrinology
Volume154
Issue number12
DOIs
Publication statusPublished - Dec 1 2013

    Fingerprint

ASJC Scopus subject areas

  • Endocrinology
  • Medicine(all)

Cite this

Gatto, F., Feelders, R., Van Der Pas, R., Kros, J. M., Dogan, F., Van Koetsveld, P. M., Van Der Lelij, A. J., Neggers, S. J. C. M. M., Minuto, F., De Herder, W., Lamberts, S. W. J., Ferone, D., & Hofland, L. J. (2013). β-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: Role in the regulation of response to somatostatin analogue treatment in patients with acromegaly. Endocrinology, 154(12), 4715-4725. https://doi.org/10.1210/en.2013-1672