GONADOTROPIN-RELEASING-HORMONE NEURONAL CELL-LINES

Gonadotropin-releasing hormone (GnRH) cell lines were developed by genetically targeted tumorigenesis in transgenic mice. The cell lines designated GT1 cells have a neuronal phenotype, express neuronal but not glial markers and express the GnRH gene at high levels. The GnRH prohormone is processed in the cells to multiple molecular forms including biologically active GnRH and GnRH-associated peptide. Basal secretion of GnRH from the cells is regulated in part by fast Na+ channels necessary for propagated action potentials. In many instances, basal GnRH release is pulsatile with an interpulse frequency similar to that seen in castrated rodents, suggesting that GnRH neurons are the pulse generator and are capable of synchronizing their secretion in vitro. The secretion of GnRH is stimulated by depolarization and by the neurotransmitter norepinephrine. In related studies we have demonstrated that expression of Simian virus 40 T antigen in GnRH neurons of transgenic mice leads to hypothalamic hypogonadism due to the inability of GnRH nerve terminals to organize in the median eminence. These findings support the use of genetically-directed tumorigenesis to establish highly differentiated GnRH neuronal cell lines that are a valuable model to study the cell biology and regulation of thc neurons.