TY - JOUR
T1 - Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas
AU - de Bruin, Christiaan
AU - Pereira, Alberto M.
AU - Feelders, Richard A.
AU - Romijn, Johannes A.
AU - Roelfsema, Ferdinand
AU - Sprij-Mooij, Diane M.
AU - van Aken, Maarten O.
AU - van der Lelij, Aart-Jan
AU - de Herder, Wouter W.
AU - Lamberts, Steven W. J.
AU - Hofland, Leo J.
PY - 2009
Y1 - 2009
N2 - Previous studies have demonstrated the expression of somatostatin receptor subtypes (mainly sst(5)) and dopamine (DA) receptor subtypes (mainly D(2)) in smaller series of human corticotroph adenomas. In line with these findings, sst(5) and D(2)-targeting agents have already been used clinically in patients with Cushing's disease (CD) and have shown promising results in subsets of patients. To what extent these receptor subtypes are coexpressed within individual adenomas, is not known however. The aim of the study was to investigate the (co-)expression of both sst and DA receptors in a large series of human corticotroph adenomas. We performed in vitro analysis of corticotroph adenoma tissue obtained via transsphenoidal adenomectomy. The study was conducted at two university medical centers. Adenoma tissue from 30 patients with CD was analyzed in this study. Analyzed by quantitative RT-PCR, D(2) and sst(5) were significantly (co-) expressed in the majority (60%) of adenomas, whereas 23% of adenomas only expressed D(2), but not sst(5). The remaining 17% of adenomas did not significantly express either sst(5) or D(2). Overall, expression of sst(1-4) and D(4) was low to nondetectable. Corticotroph adenomas with invasive growth invariably showed loss of sst(5) and D(2) expression. Autoradiography revealed clear D(2) and/or SS-14 binding in a subset of cases, which correlated well with their respective mRNA data. Sst(5) and especially D(2) are highly expressed in the majority of human corticotroph adenomas, with coexpression of sst(5) and D(2) being a common phenomenon. These findings support the current studies with sst(5) and D(2)-targeting agents in patients with CD and highlight the rationale behind sst(5)-D(2) combination therapy
AB - Previous studies have demonstrated the expression of somatostatin receptor subtypes (mainly sst(5)) and dopamine (DA) receptor subtypes (mainly D(2)) in smaller series of human corticotroph adenomas. In line with these findings, sst(5) and D(2)-targeting agents have already been used clinically in patients with Cushing's disease (CD) and have shown promising results in subsets of patients. To what extent these receptor subtypes are coexpressed within individual adenomas, is not known however. The aim of the study was to investigate the (co-)expression of both sst and DA receptors in a large series of human corticotroph adenomas. We performed in vitro analysis of corticotroph adenoma tissue obtained via transsphenoidal adenomectomy. The study was conducted at two university medical centers. Adenoma tissue from 30 patients with CD was analyzed in this study. Analyzed by quantitative RT-PCR, D(2) and sst(5) were significantly (co-) expressed in the majority (60%) of adenomas, whereas 23% of adenomas only expressed D(2), but not sst(5). The remaining 17% of adenomas did not significantly express either sst(5) or D(2). Overall, expression of sst(1-4) and D(4) was low to nondetectable. Corticotroph adenomas with invasive growth invariably showed loss of sst(5) and D(2) expression. Autoradiography revealed clear D(2) and/or SS-14 binding in a subset of cases, which correlated well with their respective mRNA data. Sst(5) and especially D(2) are highly expressed in the majority of human corticotroph adenomas, with coexpression of sst(5) and D(2) being a common phenomenon. These findings support the current studies with sst(5) and D(2)-targeting agents in patients with CD and highlight the rationale behind sst(5)-D(2) combination therapy
U2 - https://doi.org/10.1210/jc.2008-2101
DO - https://doi.org/10.1210/jc.2008-2101
M3 - Article
C2 - 19141584
SN - 0021-972X
VL - 94
SP - 1118
EP - 1124
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 4
ER -