title: Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours.
abstract: OBJECTIVE
  Adenohypophysis (AH) hormone-producing cells represent the origin of diverse groups of pituitary adenomas (PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signalling have been implicated in the aetiology of PA. Endogenous retroviruses (ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome. Some ERV genes encode open reading frames and produce functional proteins, for example, the ERVW-1 envelope gene Syncytin-1, essential for placentogenesis, but also deregulated in human tumours. Data concerning ERV expression in the AH and related endocrine tumours are missing.
  
  
  METHODS
  Syncytin-1 protein was analysed in normal AH (n = 15) and compared with five PA subtypes (n = 117) by immunohistochemistry. Absolute gene expression of 20 ERV functional envelope genes and ERVW-5 gag was measured. PA tissues were examined for Syncytin-1 and the cAMP signalling marker phospho-CREB-Ser133 using immunohistochemistry. Isolated primary human PA cells were treated with different hormones. Murine embryonic and adult pituitary gland ERV expressions were compared with human AH.
  
  
  RESULTS
  Syncytin-1 protein colocalized with corticotropic cells of AH. In contrast, all PA demonstrated significant Syncytin-1 protein overexpression, supporting deregulation. All other ERV genes showed significant up-regulations in different PA subtypes. Phospho-CREB-Ser133 and Syncytin-1 colocalized in PA cells. Cultivated primary PA cells with ACTH or CRH induced their respective receptors and ERV genes. Syncytin-A/-B, murine orthologues to human Syncytin-1/-2, localized to embryonic and adult pituitary glands demonstrating functional mammalian conservation.
  
  
  CONCLUSIONS
  Deregulated ERV genes may contribute to PA development via cAMP signalling.
authors.affiliation: Institute of Neuropathology, University-Clinic Erlangen, Lab for Molecular Medicine, Erlangen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Buslei
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Strissel
authors.forename: Christine
authors.initials: C
authors.lastname: Henke
authors.forename: Regina
authors.initials: R
authors.lastname: Schey
authors.forename: Nadine
authors.initials: N
authors.lastname: Lang
authors.forename: Matthias
authors.initials: M
authors.lastname: Ruebner
authors.forename: Claus C
authors.initials: CC
authors.lastname: Stolt
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Reiner
authors.initials: R
authors.lastname: Strick
mesh_terms: D000236:Adenoma / Q000821:virology*; D000328:Adult; D000818:Animals; D020077:Endogenous Retroviruses; D005260:Female; D005455:Fluorescent Antibody Technique; D015686:Gene Products, env / Q000096:biosynthesis; D005814:Genes, Viral; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010902:Pituitary Gland / Q000821:virology*; D010911:Pituitary Neoplasms / Q000821:virology*; D011257:Pregnancy Proteins / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin
keywords: Syncytin-1; adenohypophysis; cAMP; endogenous retrovirus (ERV); pituitary adenoma