title: Somatostatin receptor sst2 gene transfer in human prolactinomas in vitro: impact on sensitivity to dopamine, somatostatin and dopastatin, in the control of prolactin secretion.
abstract: OBJECTIVE
  As prolactinomas fail to respond to dopamine agonist (DA) in 10-20% of cases, we hypothesized that somatostatin subtype 2 receptor (sst2) overexpression in DA-resistant prolactinomas may enhance suppression of prolactine (PRL) using chimeric agonist (dopastatin) that simultaneously binds sst2 and the dopamine subtype 2 receptor (D2DR).
  
  
  METHODS
  PRL suppression by octreotide, sst5 agonist, sst2-D2DR agonist (BIM-23A760 dopastatin) and cabergoline was assessed in primary cultures of seven DA-resistant prolactinomas overexpressing sst2.
  
  
  RESULTS
  sst2 was effectively overexpressed via adenoviral expression in prolactinomas (38.1±7.4 vs. 0.1±0.1 copy/copy β-Gus) and induced octreotide sst2-mediated PRL suppression that remained lower than that induced by DA. BIM-23A760 inhibited PRL similarly to cabergoline both in the control and sst2-expressing cells. Antagonist experiments confirmed predominant dopaminergic effect in dopastatin activity.
  
  
  CONCLUSIONS
  sst2 was successfully overexpressed in prolactinomas. However BIM-23A760 was unable to enhance PRL suppression underlining a predominant dopaminergic contribution in its action.
authors.affiliation: Aix-Marseille University, CRN2M, UMR 7286-CNRS, 51, Bd Pierre Dramard, 13344 Marseille, France. t.cuny@chu-nancy.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuny
authors.forename: Amira
authors.initials: A
authors.lastname: Mohamed
authors.forename: Thomas
authors.initials: T
authors.lastname: Graillon
authors.forename: Catherine
authors.initials: C
authors.lastname: Roche
authors.forename: Céline
authors.initials: C
authors.lastname: Defilles
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Germanetti
authors.forename: Bettina
authors.initials: B
authors.lastname: Couderc
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Alain
authors.initials: A
authors.lastname: Enjalbert
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
authors.forename: Alexandru
authors.initials: A
authors.lastname: Saveanu
mesh_terms: D000256:Adenoviridae; D000293:Adolescent; D000328:Adult; D000077465:Cabergoline; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D015282:Octreotide / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000235:genetics; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; D013004:Somatostatin; D011388:Prolactin; C531242:TBR-760; D000077465:Cabergoline; D015282:Octreotide; D004298:Dopamine