Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
We performed in vitro analysis of corticotroph adenoma tissue obtained via transsphenoidal adenomectomy.


METHODS
The study was conducted at two university medical centers.


METHODS
Adenoma tissue from 30 patients with CD was analyzed in this study.


RESULTS
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.


CONCLUSIONS
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.
de Bruin
Christiaan
C
Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. c.debruin@erasmusmc.nl
Pereira
Alberto M
AM
Feelders
Richard A
RA
Romijn
Johannes A
JA
Roelfsema
Ferdinand
F
Sprij-Mooij
Diane M
DM
van Aken
Maarten O
MO
van der Lelij
Aart-Jan
AJ
de Herder
Wouter W
WW
Lamberts
Steven W J
SW
Hofland
Leo J
LJ
D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics*; D055815:Young Adult
D017931:DNA Primers; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin