Biology of hypothalamic neurons producing gonadotropin-releasing hormone (GnRH): new information on the use of immortalized cells secreting GnRH

The study of the neurons secreting the gonadotropin releasing hormone (GnRH), the hypothalamic hormone stimulating the release of pituitary gonadotropins, has been potentiated by the development of immortalized cells that specifically synthetize and secrete GnRH. Two cell lines have been obtained by targeted tumorigenesis in transgenic mice: 1) the GT1 cells (with GT1-1, GT1-3 and GT1-7 subclones), and 2) the GN cells (with the GN10, GN11 and NLT subclones). GT1 cells have been obtained from a hypothalamic tumor and exhibit the properties of fully mature GnRH secreting neurons after they reached their final destination in the hypothalamus starting from the olfactory placode. Because of their characteristics GT1 cells have been mainly utilized to investigate the secretory properties of GnRH neurons and to identify the inputs modulating their activity. By this way a consistent number of receptors responding to specific ligands (neurotransmitters, hormones, growth factors) controlling GnRH synthesis and secretion has been identified. GN cells have been derived from a tumor of the olfactory bulb and are considered to replicate the properties of immature GnRH secreting neurons still retaining the capacity of moving. Consequently these cells are used to identify and characterize the factors influencing the migratory process of GnRH neurons from the olfactory placode to the hypothalamus. It has been found that factors stimulating GnRH neuron motility include anosmin, the protein encoded by the KAL1 gene, whose mutations lead to the form of hypogonadotropic hypogonadism known as Kallmann’s syndrome, growth factors such as fibroblast growth factor, hepatocyte growth factor, vascular endothelial growth factor, and cytoskeleton associated proteins (stathmin). On the contrary GABA agonists and glucocorticoids depress GN cells motility. As a whole the findings reported in this review seem particularly important to provide further information on the central mechanisms controlling development and function of the reproductive system.