Lipopolysaccharide increases γ-aminobutyric acid synthesis in medial preoptic neurones in association with inhibition of steroid-induced luteinising hormone surge in female rats

Lipopolysaccharide (LPS), an endotoxin produced by Gram-negative bacteria, inhibits gonadotrophin secretion and ovulation in female mammals. The present study was undertaken to examine whether gamma-aminobutyric acid (GABA)-synthesising neurones in the medial preoptic area (mPOA) may be involved in the inhibition by LPS of progesterone-induced luteinising hormone (LH) surge in ovariectomised oestrogen-primed rats. An intravenous injection of LPS (10 mu g) at noon significantly increased the content of glutamic acid decarboxylase 67 (GAD67), a GABA-synthesising enzyme, in brain tissues including the mPOA. LPS treatment also significantly increased the number of detectable GAD67-immunoreactive (ir) as well as GABA-ir cells in the mPOA, compared to control rats. The same LPS challenge completely eliminated the steroid-induced LH surge, which was normally induced in control rats in the afternoon. A local injection of muscimol (100 ng), a GABA(A) receptor agonist, into the mPOA also significantly attenuated the LH surge, mimicking the effect of LPS. These results suggest that LPS stimulates GABA synthesis in preoptic neurones, which in turn inhibit the LH surge in female rats. The results also support the hypothesis that diminution of the GABAergic suppressive activity in the mPOA permits the LH surge to be induced.