Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro.
Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro.
复制标题
一氧化氮在体内和体外控制黄体生成素释放激素释放中的作用。
DOI：
10.1073/pnas.90.21.10130
复制
发表时间：
1993
影响因子：
11.1
通讯作者：
McCann,SM
中科院分区：
文献类型：
--
作者：
Rettori,V;Belova,N;Dees,WL;Nyberg,CL;Gimeno,M;McCann,SM
一氧化氮（NO）合酶是一种将精氨酸转化为瓜氨酸加NO（一种高度活性的自由基）的酶，已在大脑中的许多神经元（包括下丘脑中的神经元）中发现。我们以前的实验表明，去甲肾上腺素诱导的前列腺素E2释放从体外培养的下丘脑外植体是由NO介导的。由于释放的促黄体生成素释放激素（LHRH）也是由去甲肾上腺素和前列腺素E2驱动，我们假设，NO也可能控制脉冲释放的LHRH在体内，从而导致在脉冲释放促黄体生成素（LH）。为了确定NO在体内控制脉冲式LH释放中的作用，将NO合酶抑制剂NG-单甲基-L-精氨酸（NMMA）在0和60 min后微量注射到清醒去势雄性大鼠的第三脑室（1 mg/5 μ L）;在此期间每10 min采集一次血样。NMMA阻断脉冲式LH释放20分钟内，血浆LH浓度进一步下降，在60分钟注射后没有脉冲。脉冲式LH释放没有改变稀释剂注射对照。NMMA没有改变卵泡刺激素的脉冲式释放，这表明其释放不需要NO。用去甲肾上腺素（10 μ M）孵育内侧基底下丘脑诱导LHRH释放增加，NMMA（300 μ M）抑制LHRH释放。NMMA单独没有改变基础LHRH释放，而硝普钠（100 μ M），自发释放NO增加。这种增加被血红蛋白（2微克/毫升）阻止，它结合了硝普钠释放的NO。我们以前的实验表明，去甲肾上腺素诱导的前列腺素E2的释放是由NO介导的。一氧化氮能神经元在正中隆起附近的LHRH终末可视化。结合在体内和体外的结果表明，由去甲肾上腺素诱导的LHRH的脉冲释放所带来的α 1-肾上腺素能激活NO合酶。然后，NO诱导前列腺素E2释放，前列腺素E2激活LHRH分泌颗粒的胞吐作用进入门静脉血管，以诱导脉冲式LH释放。
Nitric oxide (NO) synthase, the enzyme which converts arginine into citrulline plus NO, a highly active free radical, has been found in many neurons in the brain, including neurons in the hypothalamus. Our previous experiments showed that norepinephrine-induced prostaglandin E2 release from hypothalamic explants incubated in vitro is mediated by NO. Since the release of luteinizing hormone-releasing hormone (LHRH) is also driven by norepinephrine and prostaglandin E2, we hypothesized that NO might also control pulsatile release of LHRH in vivo, resulting in turn in pulsatile release of luteinizing hormone (LH). To ascertain the role of NO in control of pulsatile LH release in vivo, an inhibitor of NO synthase, NG-monomethyl-L-arginine (NMMA), was microinjected into the third cerebral ventricle (1 mg/5 microliters) of conscious castrate male rats at time 0 and 60 min later; blood samples were taken every 10 min during this period. NMMA blocked pulsatile LH release within 20 min, and plasma LH concentration declined further without pulses after the injection at 60 min. Pulsatile release of LH was not altered in diluent-injected controls. NMMA did not alter pulsatile release of follicle-stimulating hormone, which suggests that its release does not require NO. Incubation of medial basal hypothalami with norepinephrine (10 microM) induced an increase in LHRH release that was inhibited by NMMA (300 microM). NMMA alone did not alter basal LHRH release, whereas it was augmented by sodium nitroprusside (100 microM), which releases NO spontaneously. This augmentation was prevented by hemoglobin (2 micrograms/ml), which binds the NO released by nitroprusside. Our previous experiments showed that norepinephrine-induced release of prostaglandin E2 is mediated by NO. Nitric oxidergic neurons were visualized in the median eminence adjacent to the LHRH terminals. The combined in vivo and in vitro results indicate that the pulsatile release of LHRH induced by norepinephrine is brought about by alpha 1-adrenergic activation of NO synthase. NO then induces prostaglandin E2 release that activates exocytosis of LHRH secretory granules into the portal vessels to induce pulsatile LH release.