Glutamatergic regulation of gonadotropin releasing hormone mRNA levels during development in the mouse

The aims of these studies were to investigate the time course of the increase in gonadotropin releasing hormone (GnRH) mRNA levels during sexual development in the mouse, and to test the hypothesis that the neurotransmitter glutamate regulates the GnRH secretory system via actions at the level of GnRH gene expression. GnRH mRNA abundance was estimated by measuring silver grains generated by in situ hybridization of an S-35-labelled oligonucleotide probe. There was a significant increase in GnRH mRNA abundance between the day of birth (P0) and postnatal day 2 (P2) in male mice, but no further increases at later ages when overt pubertal changes are manifest. GnRH mRNA levels also increased significantly between P0 and P2 in female mice. Treatment with the glutamate agonist NMDA caused a significant increase in GnRH mRNA levels in neonatal (P0) mice and adult male mice within 30 min of treatment, which is consistent with previous studies in the rat implicating glutamate in the regulation of GnRH mRNA stability. Treatment with the glutamate antagonist CGP40116 caused an equally rapid decrease in GnRH mRNA levels in adult mice and in mice on P5 after the neonatal increase in GnRH gene expression, but was without effect in mice on P0, prior to the developmental increase. These observations that the effect on GnRH mRNA levels of blocking endogenous glutamatergic signalling depends upon the developmental stage suggest that endogenous glutamate maintains GnRH mRNA levels in adult mouse, and is a potential regulator of the developmental increase seen in the neonatal period.