Immortalization of Hypothalamic Gonadotropin-Releasing Hormone Neurons Using Targeted Oncogene Expression in Transgenic Mice

Three clonal gonadotropin-releasing hormone (GnRH) neuronal cell lines were derived from a genetically induced tumor in transgenic mice. A transgene was constructed to target expression of simian virus 40 T antigen to GnRH neurons using the promoter/enhancer domains of the cell-specifically expressed GnRH gene. The resulting GT1 cells were characterized by morphology, the expression of neuron-specific genes, expression and processing of GnRH, pulsatile basal secretion of GnRH, release of GnRH in response to depolarization, and regulation of GnRH release by a variety of neurotransmitters and neuromodulators. By all of these criteria, GT1 cells are highly differentiated neuronal cell lines that provide valuable models for studying the cell biology of neuroendocrine cells.