title: Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors.
abstract: Ghrelin is a novel gastrointestinal hormone produced by rat and human gastric X-like neuroendocrine cells, which strongly stimulates GH secretion and influences energy balance, gastric motility, and acid secretion. Ghrelin is expressed in pituitary and gastrointestinal endocrine tumors. It binds to the GH secretagogue receptor (GHS-R), which is present in a wide variety of central and peripheral human tissues. The aim of the present study was 2-fold: 1) to determine, by immunohistochemistry and mRNA analysis, whether pancreatic islet cells produce ghrelin and express GHS-R; and 2) to investigate ghrelin and GHS-R expression in pancreatic endocrine tumors. Seven cases of nonneoplastic pancreatic tissue and 28 endocrine tumors were studied. In pancreatic islets, ghrelin immunoreactivity was present in all cases and confined to beta-cells. Eleven of the 28 (39%) endocrine tumors were immunoreactive for ghrelin. In situ hybridization and RT-PCR confirmed the immunohistochemical data for both tumors and islets but also revealed ghrelin mRNA in 8 and 11 additional tumors, respectively. GHS-R 1a and 1b mRNAs were present in 7 of 28 and 14 of 28 tumors, respectively, studied by RT-PCR. These findings demonstrate that ghrelin production is not restricted to the stomach but is also present in pancreatic beta-cells and endocrine tumors (regardless of the type of pancreatic hormone produced, if any). Expression of GHS-R in some of the endocrine tumors studied indicates that autocrine/paracrine circuits may be active in neoplastic conditions.
authors.affiliation: Department of Biomedical Sciences and Oncology, University of Turin, I-10126 Torino, Italy. mauro.papotti@unito.it
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Elena
authors.initials: E
authors.lastname: Allìa
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gugliotta
authors.forename: Ada
authors.initials: A
authors.lastname: Funaro
authors.forename: Fabio
authors.initials: F
authors.lastname: Broglio
authors.forename: Romano
authors.initials: R
authors.lastname: Deghenghi
authors.forename: Giampiero
authors.initials: G
authors.lastname: Muccioli
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D054439:Ghrelin; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D036361:Peptide Hormones; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin