title: Ghrelin and obestatin in human neuroendocrine tumors: expression and effect on obestatin levels after food intake.
abstract: BACKGROUND
  Ghrelin and obestatin are derived from the same peptide hormone precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in many biological processes, whereas the physiological function of obestatin needs further investigation. The aims of the present study were to establish the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs) and to investigate if blood obestatin concentrations are influenced during a standardized meal stimulation test in healthy individuals and patients with NETs.
  
  
  METHODS
  The expression of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine-related disorders (n = 3) using immunohistochemistry with specific polyclonal antibodies. Coexpression of the peptides was evaluated by double immunofluorescence. Concentrations of obestatin in blood were measured during a meal test in 6 healthy individuals and 5 patients with pancreatic NETs.
  
  
  RESULTS
  Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues, respectively, mainly representing NETs of foregut origin and in pancreatic tissue from a nesidioblastosis patient. Double immunofluorescence staining showed colocalization of the peptides. During the meal test, obestatin levels in blood were unchanged in all patients but decreased significantly in the healthy individuals.
  
  
  CONCLUSIONS
  Only a minority of NETs express ghrelin and obestatin. However, analysis of patients with tumors originating from tissues that express the peptides in normal conditions could be of importance. The results from the meal test indicate that the hormone levels are affected by food intake in healthy individuals, whereas obestatin levels remained unchanged in pancreatic NET patients.
authors.affiliation: Section of Endocrine Oncology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. malin.gronberg @ medsci.uu.se
authors.forename: Malin
authors.initials: M
authors.lastname: Grönberg
authors.forename: Apostolos V
authors.initials: AV
authors.lastname: Tsolakis
authors.forename: Ulf
authors.initials: U
authors.lastname: Holmbäck
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Lars
authors.initials: L
authors.lastname: Grimelius
authors.forename: Eva T
authors.initials: ET
authors.lastname: Janson
mesh_terms: D000328:Adult; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004435:Eating / Q000502:physiology*; D054439:Ghrelin / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013274:Stomach Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D004040:Dietary Carbohydrates; D054439:Ghrelin; C505799:obestatin, human