Kainate receptor subunit-positive gonadotropin releasing hormone neurons express c-fos during the steroid-induced luteinizing female rat

During the preovulatory and estradiol-progesterone-induced GnRH-LH surge, a subpopulation of GnRH neurons transiently expresses the transcription fact or c-fos, which is a useful marker of cell activation. To further character ize this subpopulation of GnRH neurons, multiple immunohistochemical proced ures were applied to visualize GnRH, c-Fos, KA2, GluR5, GluR6, and GluR7 re ceptor subunits during different phases of the estrogen-progesterone-induce d LH surge. The results show that the LH surge begins at 1400 h and peaks a t 1600 h before returning to baseline late in the evening. At 1400 h, about 50% of the GnRH neurons contained c-Fos, and this percentage remained high at 65% at 1600 and 2000 h. During the surge, 50% of the c-Fos-positive GnR H neurons contained KA2 receptor subunit protein at 1400 h, 65% of the c-Fo s-positive GnRH neurons expressed the KA2 subunit at 1600 h, and 50% of the c-Fos-positive GnRH neurons expressed the KA2 subunit at 2000 h. As KA2 su bunits require other kainate-preferring subunits to form functional recepto r channels, we examined GnRH neurons for the presence of GluR5, GluR6, and GluR7 messenger RNA (mRNA) and protein. The results show that the KA2-conta ining GnRH neurons also contain GluR5 receptor subunit mRNA and protein, an d that these GnRH neurons are c-Fos positive during the steroid-induced LH surge. To determine whether administration of kainate is sufficient to induce c-Fo s in GnRH neurons, steroid-primed animals received iv injections of subseiz ure-inducing amounts of kainic acid and were processed for immunohistochemi stry and in situ hybridization. The results show that kainic acid causes a significant increase in circulating LH; however, it does not induce c-Fos i n GnRH neurons, nor does it cause an increase in GnRH mRNA. Together, the results suggest that a large subset of GnRH neurons expresses KA2 as well as GluR5 receptor subunits, which would allow the formation of functional glutamate receptor channels, and that this subset of GnRH neuro ns is activated during the steroid-induced LH surge.