Prostaglandins (PGs), especially PGE2, are among the essential mediators involved in the regulation of gonadotropin secretion. The effect of PGE2 is assumed, at least in part, to be a consequence of its action on gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. We previously reported that cyclooxygenase-1, the key enzyme in the synthesis of PGs, is associated with the accumulation of GnRH and is expressed exclusively in microglia in the preoptic area (POA) where GnRH neural perikarya are mainly located in ovariectomized ovarian steroid-primed rats. In this study, we examined whether PGs can affect electrophysiological properties of GnRH neural perikarya in the POA. Effects of ovarian steroids on the modulatory action of PGs were also investigated. Whole-cell patch-clamp recordings were performed to analyze miniature excitatory postsynaptic currents (mEPSCs) in GnRH neurons in the POA slices prepared from female GnRH-EGFP rats (kindly provided by Drs. Kato and Sakuma, Nippon Medical School). PGE2 was applied in the perfusion medium. In intact rats, PGE2 treatment significantly increased the frequency of mEPSCs of GnRH neurons on the day of proestrus, but slightly reduced it on the day of diestrus 1. Similarly, the frequency of mEPSCs of GnRH neurons was significantly increased by PGE2 in the estrogen-primed, but not the sesame oil-treated, ovariectomized rats. The amplitude of mEPSCs of GnRH neurons was not affected by PGE2 in any groups. Vehicle (ethanol) did not affect either the frequency or the amplitude of mEPSCs of GnRH neurons. These findings show that PGE2 can affect electrophysiological properties of GnRH neurons in the POA probably by acting at presynaptic site(s), and the effect is dependent on ovarian steroid environments.