Lipopolysaccharide increases γ-aminobutyric acid synthesis in medial preoptic neurones in association with inhibition of steroid-induced luteinising hormone surge in female rats
Lipopolysaccharide increases γ-aminobutyric acid synthesis in medial preoptic neurones in association with inhibition of steroid-induced luteinising hormone surge in female rats
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DOI：
10.1111/j.1365-2826.2005.01358.x
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发表时间：
2005-10-01
影响因子：
3.2
通讯作者：
Sugiyama, H
中科院分区：
文献类型：
--
作者：
Akema, T;He, D;Sugiyama, H
脂多糖（LPS）是革兰氏阴性菌产生的一种内毒素，可抑制雌性哺乳动物促性腺激素分泌和排卵。本研究旨在探讨内侧视前区（mPOA）γ-氨基丁酸（GABA）合成神经元是否参与脂多糖（LPS）抑制去卵巢雌激素诱导的促黄体生成激素（LH）峰。中午静脉注射LPS（10 μ g）显著增加了包括mPOA在内的脑组织中谷氨酸脱羧酶67（GAD 67）（GABA合成酶）的含量。与对照组大鼠相比，LPS治疗还显著增加了mPOA中可检测到的GAD 67免疫反应（IR）以及GABA-IR细胞的数量。同样的LPS激发完全消除了类固醇诱导的LH峰，这通常是在下午在对照大鼠中诱导的。在mPOA内局部注射蝇蕈醇（100 ng）（一种GABA（A）受体激动剂）也能明显减弱LH峰，类似于LPS的作用。这些结果表明，LPS刺激视前神经元GABA的合成，从而抑制LH峰在雌性大鼠。结果还支持了mPOA中GABA能抑制活性的减弱可以诱导LH激增的假设。
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.