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ß-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.

Authors: Gatto, Federico  Feelders, Richard  van der Pas, Rob  Kros, Johan M  Dogan, Fadime  van Koetsveld, Peter M  van der Lelij, Aart-Jan  Neggers, Sebastian J C M M  Minuto, Francesco  de Herder, Wouter  Lamberts, Steven W J  Ferone, Diego  Hofland, Leo J 
Citation: Gatto F, etal., Endocrinology. 2013 Dec;154(12):4715-25. doi: 10.1210/en.2013-1672. Epub 2013 Oct 29.
Pubmed: (View Article at PubMed) PMID:24169548
DOI: Full-text: DOI:10.1210/en.2013-1672

Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK)2 and ß-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and ß-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, ß-arrestin 1, and ß-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. ß-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 ß-arrestin 1 (P < .05) and positively correlated to ß-arrestin 2 (P < .0001). SSA treatment did not affect GRK2 and ß-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, ß-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, ß-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, ß-arrestin 1, and ß-arrestin 2 expression in a representative number of pituitary adenomas. ß-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.

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CRRD Object Information
CRRD ID: 13792706
Created: 2018-09-21
Species: All species
Last Modified: 2018-09-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.