title: Glial cell line-derived neutrotrophic factor and neurturin can act as paracrine growth factors stimulating DNA synthesis of Ret-expressing spermatogonia.
abstract: Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are related growth factors which exert trophic effects on several neuronal populations and developing kidney. GDNF-family ligands interact with membrane receptors designated GFRalphas which, in turn, mediate stimulation of the Ret receptor tyrosine kinase. Here we show that Ret, GFRalpha-1 (the GDNF receptor), and GFRalpha-2 (the NTN receptor) are expressed by testicular germ cells, while GDNF and NTN are expressed by Sertoli cells. Both GDNF and NTN stimulate DNA synthesis in spermatogonia. Furthermore, Ret, ligands and co-receptors are expressed in germ cell tumors. Thus, GDNF-family ligands may act as paracrine factors in spermatogenesis and this circuit may be active in germ cell tumors.
authors.affiliation: Istituto Nazionale dei Tumori di Napoli, 80131 Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Viglietto
authors.forename: S
authors.initials: S
authors.lastname: Dolci
authors.forename: P
authors.initials: P
authors.lastname: Bruni
authors.forename: G
authors.initials: G
authors.lastname: Baldassarre
authors.forename: L
authors.initials: L
authors.lastname: Chiariotti
authors.forename: R M
authors.initials: RM
authors.lastname: Melillo
authors.forename: G
authors.initials: G
authors.lastname: Salvatore
authors.forename: G
authors.initials: G
authors.lastname: Chiappetta
authors.forename: F
authors.initials: F
authors.lastname: Sferratore
authors.forename: A
authors.initials: A
authors.lastname: Fusco
authors.forename: M
authors.initials: M
authors.lastname: Santoro
mesh_terms: D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D029721:Drosophila Proteins; D018237:Germinoma / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000032:analysis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D013093:Spermatogonia / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C495039:GDNF protein, human; C494987:GFRA1 protein, human; C495040:Gdnf protein, mouse; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C495053:NRTN protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495056:Nrtn protein, mouse; D011518:Proto-Oncogene Proteins; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse