title: Characterization of MENX-associated pituitary tumours.
abstract: OBJECTIVE
  The aim of this study is to evaluate the pathological features, serum hormone levels and ex vivo cultures of pituitary adenomas that occur in rats affected by MENX syndrome. MENX is multiple endocrine neoplasia syndrome caused by a germline mutation in the cell cycle inhibitor p27. Characterization of MENX adenomas is a prerequisite to exploit this animal model for molecular and translational studies of pituitary adenomas.
  
  
  METHODS
  We investigated MENX pituitary adenomas with immunohistochemistry, double immunofluorescence, electron microscopy, reverse transcription polymerase chain reaction (RT-PCR), measurement of serum hormone levels and ex vivo cultures.
  
  
  RESULTS
  Adenomas in MENX rats belong to the gonadotroph lineage. They start from 4 months of age as multiple neoplastic nodules and progress to become large lesions that efface the gland. Adenomas are composed of chromophobic cells predominantly expressing the glycoprotein alpha-subunit (αGSU). They show mitotic activity and high Ki67 labelling. A few neoplastic cells co-express gonadotropins and the transcription factor steroidogenic factor 1, together with growth hormone or prolactin and Pit-1, suggesting that they are not fully committed to one cell lineage. Ex vivo cultures show features similar to the primary tumour.
  
  
  CONCLUSIONS
  Our results suggest that p27 function is critical to regulate gonadotroph cells growth. The MENX syndrome represents a unique model to elucidate the physiological and molecular mechanisms mediating the pathogenesis of gonadotroph adenomas.
authors.affiliation: Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Marinoni
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Mountford
authors.forename: A
authors.initials: A
authors.lastname: Perren
authors.forename: I
authors.initials: I
authors.lastname: Bravi
authors.forename: L
authors.initials: L
authors.lastname: Jennen
authors.forename: A
authors.initials: A
authors.lastname: Feuchtinger
authors.forename: J
authors.initials: J
authors.lastname: Drouin
authors.forename: F
authors.initials: F
authors.lastname: Roncaroli
authors.forename: N S
authors.initials: NS
authors.lastname: Pellegata
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006062:Gonadotropins / Q000235:genetics; D007150:Immunohistochemistry; D009377:Multiple Endocrine Neoplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006062:Gonadotropins; D050760:Cyclin-Dependent Kinase Inhibitor p27