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
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| Citation: |
Gatto F, etal., Endocrinology. 2013 Dec;154(12):4715-25. doi: 10.1210/en.2013-1672. Epub 2013 Oct 29. |
| RGD ID: |
13792706 |
| Pubmed: |
PMID:24169548 (View Abstract at PubMed) |
| DOI: |
DOI:10.1210/en.2013-1672 (Journal Full-text) |
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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| Genes (Rattus norvegicus) |
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| Grk2 (G protein-coupled receptor kinase 2) |
| Genes (Mus musculus) |
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| Grk2 (G protein-coupled receptor kinase 2) |
| Genes (Homo sapiens) |
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| GRK2 (G protein-coupled receptor kinase 2) |
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