Role of glucocorticoid receptors in mouse neurons secreting gonadotropin releasing hormone

Glucocorticoid receptors (GR) are present in hypotha- lamic neurons secreting gonadotropin releasing hormone (GnRH), suggesting a direct effect of glucocorticoids (Gc) in the control of the synthesis, and/or release of the neuro- hormone. This hypothesis has been confirmed by previous results from our laboratory indicating the presence of GR in the so called GT1-7 cells, an immortalized cell line mim- icking the properties of mature hypothalamic GnRH secreting neurons. The experiments here summarized have been addressed to analyze whether: (1) GR are present also in GN11 immortalized GnRH neurons that are thought to replicate the characteristics of immature GnRH secreting neurons still migrating from the olfactory placode to the hypothal- amus, and (2) whether the activation of GR has some influence on the organization and migratory capacity of GN11 cells. The results obtained show that: (1) experi- ments performed through the means of receptor binding assay, RT-PCR, immunocytochemistry and immunoblot- ting techniques, demonstrate that GR are present also in GN11 cells, as demonstrated by the binding of dexa- methasone (Dex), the prototypic synthetic GC, to cytosol- ic preparations of GN11 cells; (2) the activation of GR by the addition of Dex to GN11 cells induces nuclear trans- location of GR but does not lead to the inhibition of GnRH gene expression already reported in GT1-7 cells; (3) long-term exposure of GN11 cells to Dex induces a transdifferentiation of the cells towards an epithelial-like phenotype with a reorganization of F-actin in stress fibers; (4) Dex treatment significantly decreases the migra- tory activity of the cells induced in vitro by the addition of fetal bovine serum; (5) finally, Dex addition brings about in GN11 cells an increase of the levels of phosphor- ylated focal adhesion kinase, an index of extracellular matrix function. In conclusion, the data here reported suggest that GR are expressed in hypothalamic GnRH neurons in vivo as well as in mature and immature GnRH secreting neurons in vitro. The different effects displayed by Dex on GN11 cells motility and morphology could suggest that glucocorticoids are involved in the processes regulating the migration of GnRH secreting neurons from the olfactory placode to their final localization in the hypothalamus. This seems to include some modification of the cytoskeleton and shape of GnRH neurons as well as of the extracellular matrix.