Glial cell line-derived neutrotrophic factor and neurturin can act as paracrine growth factors stimulating DNA synthesis of Ret-expressing spermatogonia

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are related growth factors which exert trophic effects on several neuronal popu lations and developing kidney. GDNF-family ligands interact with membrane r eceptors designated GFR alpha s which, in turn, mediate stimulation of the Ret receptor tyrosine kinase. Here we show that Ret, GFR alpha-1 (the GDNF receptor), and GFR alpha-2 (the NTN receptor) are expressed by testicular g erm cells, while GDNF and NTN are expressed by Sertoli cells. Both GDNF and NTN stimulate DNA synthesis in spermatogonia. Furthermore, Ret, ligands an d co-receptors are expressed in germ cell tumors. Thus, GDNF-family ligands may act as paracrine factors in spermatogenesis and this circuit may be ac tive in germ cell tumors.