Mechanisms mediating the response of GnRH neurones to excitatory amino acids

Excitatory amino acids, such as glutamate, exert a profound stimulatory effect on the reproductive axis of several mammals. Although glutamate receptor agonists stimulate GnRH secretion, both in vivo and in vitro, it is unclear whether GnRH neurones respond directly to glutamatergic excitation. Immortalized GnRH neurones (GT1 cells) express glutamate receptors when grown in culture and also show enhanced GnRH secretion in response to glutamate receptor agonists. In addition, immunocytochemical evidence at the electron microscope level supports the possibility of a direct interaction between glutamatergic and GnRH neurones. In general, however, double-label histochemical studies (using immunocytochemistry, in situ hybridization, or a combination of these techniques) have not shown significant glutamate receptor gene expression in GnRH neurones of adult animals. It remains to be determined whether a higher degree of glutamate receptor gene expression occurs during development. This general lack, or very low amount, of glutamate receptor gene expression in the GnRH neurones of adults supports the view that excitatory amino acids exert their stimulatory action on the reproductive axis primarily through interneuronal pathways that impinge on the GnRH neurones, rather than by stimulating GnRH release directly.