細菌性内毒素によるゴナドトロピン分泌抑制におけるGABA及びCRFの関与

We have reported that that bacterial endotoxin (lipopolysaccharide, LPS) interacts with opioid and excitatory amino acid inputs to gonadotropin-releasing hormone (GnRH) neurons to inhibit luteinzing hormone (LH) release in ovariectomized rats. The aim of this study was to examine possible roles of GABA and CRF in LPS-induced inhibition of LH release. Pretreatment with LPS (10ug/rat, iv), which did not affect the basal LH release by itself, significantly inhibited the steroid-induced LH surge. LPS also reduced Fos expression in GnRH neurons, and significantly increased the number of GABA immunoreactive cells in the mPOA. But no significant difference was detected in the number of CRF neurons in the PVN between the LPS-treated and control rats. Local, injection of muscimol (a GABA-A receptor agonist, 0.1ug/rat) into the mPOA significantly inhibited the steroid-induced LH surge. These results suggest that LPS might stimulate preoptic GABA neurons, either directly or indirectly, which, in turn, suppresse the activity of GnRH neurons, resulting in the inhibition of LH surge. As far as the number of CRF neurons is concerned, we could not obtain evidence for an involvement of CRF in LPS-induced suppression of gonadotropin release. Father studies on the influence of LPS on Fos expression in CRF neurons are necessary. [Jpn J Physiol 54 Suppl:S222 (2004)]