Estrogen Modulates Effects of Glutamate on In Vitro Gonadotropin-Releasing Hormone Release by Altering Nitric Oxide Action in Female Rats

Abstract

The present study aimed to determine whether nitric oxide (NO) mediates the effect of glutamate on gonadotropin-releasing hormone (GnRH) release from the arcuate nucleus-median eminence, and whether estrogen modulates the NO action. Arcuate nucleus-median eminence fragments taken from ovariectomized (OVX) or estradiol-primed OVX rats were incubated in a medium containing glutamate with or without N^Gmonomethyl-L-arginine (NMMA), an nitric oxide synthase inhibitor, or hemoglobin (Hb), an NO scavenger. Cyclic guanosine 3', 5'-monophosphate (cGMP) levels in tissue fragments were also measured. Glutamate induced GnRH release in the estradiol-primed OVX group. The glutamate-induced GnRH release was reduced by NMMA or Hb without a significant change in cGMP levels. In the OVX group, glutamate did not increase GnRH release, but the release was stimulated by combination with NMMA or Hb. The cGMP level was increased by glutamate and this increase was reduced by Hb or NMMA. These results suggest that NO has both stimulatory and inhibitory effects on glutamate-induced GnRH release from the arcuate nucleus-median eminence fragments, and that estrogen alters the NO actions to modulate the glutamate-induced GnRH release.