TY - JOUR
T1 - beta-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
AU - Gatto, Federico
AU - Feelders, R.A.
AU - Pas, Rob
AU - Kros, J.M.
AU - Dogan - Oruç, Fadime
AU - van Koetsveld, Peter
AU - Lelij, Aart Jan
AU - Neggers, S.J.C.M.M.
AU - Minuto, F
AU - de Herder, W.W.
AU - Lamberts, S.W.J.
AU - Ferone, D
AU - Hofland, Leo
PY - 2013
Y1 - 2013
N2 - Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK) 2 and beta-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and beta-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, beta-arrestin 1, and beta-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. beta-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 beta-arrestin 1 (P < .05) and positively correlated to beta-arrestin 2 (P < .0001). SSA treatment did not affect GRK2 and beta-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, beta-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, beta-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, beta-arrestin 1, and beta-arrestin 2 expression in a representative number of pituitary adenomas. beta-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.
AB - Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK) 2 and beta-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and beta-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, beta-arrestin 1, and beta-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. beta-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 beta-arrestin 1 (P < .05) and positively correlated to beta-arrestin 2 (P < .0001). SSA treatment did not affect GRK2 and beta-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, beta-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, beta-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, beta-arrestin 1, and beta-arrestin 2 expression in a representative number of pituitary adenomas. beta-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.
U2 - 10.1210/en.2013-1672
DO - 10.1210/en.2013-1672
M3 - Article
SN - 0013-7227
VL - 154
SP - 4715
EP - 4725
JO - Endocrinology
JF - Endocrinology
IS - 12
ER -