title: Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. c.debruin@erasmusmc.nl
authors.forename: Christiaan
authors.initials: C
authors.lastname: de Bruin
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.forename: Diane M
authors.initials: DM
authors.lastname: Sprij-Mooij
authors.forename: Maarten O
authors.initials: MO
authors.lastname: van Aken
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lelij
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
mesh_terms: 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
chemical_list: D017931:DNA Primers; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin