Central regulation of luteinizing hormone-releasing hormone release by nitric oxide in female rsts.

一氧化氮(NO)是一种新的可扩散的细胞间或细胞内信使，是调节下丘脑LHRH释放的因子之一。最近的研究表明，雌激素在体外调节兴奋性氨基酸诱导的大鼠弓状核-正中隆起(ARC-ME)片段释放LHRH。因此，本研究旨在测试雌激素是否通过改变NO的作用而调节体外谷氨酸诱导的LHRH的释放，以及NO的作用部位在哪里。取去卵巢(OVX)、去卵巢(OVX)和雌二醇刺激(OVX)大鼠的ARC-ME或ME片段，分别与谷氨酸、NO清除剂N-甲基-L-精氨酸(NMMA)或血红蛋白(Hb)共同孵育3min，或与NO供体硝普钠(SNP)共同孵育3min。在孵育结束时，将组织碎片匀浆以测量…CGMP含量较多。在体外，与不改变cGMP含量的单独谷氨酸处理相比，谷氨酸和NMMA共同孵育OVX和OVX E2大鼠的ME片段的LHRH释放显著增加。NO对谷氨酸诱导的去卵巢大鼠ARC-ME片段和ME片段释放LHRH似乎也有抑制作用。进一步发现谷氨酸可增加去势大鼠ARC-ME片段中cGMP的水平，NMMA或Hb可阻断谷氨酸诱导的cGMP升高。另一方面，NMMA或Hb可完全抑制谷氨酸诱导的去卵巢大鼠ARC-ME片段释放LHRH，而不是通过cGMP的产生。这些结果清楚地表明，雌激素在体外通过改变介导谷氨酸作用的NO音调来调节谷氨酸诱导的ARC-ME片段释放LHRH。另一方面，在谷氨酸诱导的ME片段释放LHRH的过程中，NO起抑制作用。这些结果还表明，NO以雌激素依赖的方式在ARC-ME或ME区介导谷氨酸对LHRH释放的作用，并且在谷氨酸诱导的LHRH释放中具有双重作用：一种是刺激作用，另一种是抑制作用。此外，NO本身似乎直接参与了在雌激素存在的情况下诱导ARC-ME和ME片段释放LHRH，但在没有雌激素的情况下不是通过cGMP的产生，因为SNP诱导的OVX E2大鼠ARC-ME和ME片段的LHRH释放可被Hb阻断，而不改变cGMP的含量。综上所述，本研究提示NO介导了谷氨酸盐对ARC-ME操作区LHRH释放的影响，雌激素改变了NO对LHRH释放的影响。因此，NO可能通过传递雌激素对刺激性雌激素的抑制作用，在ARC的雌激素反馈机制中发挥重要作用。较少

Nitric oxide (NO), a novel diffusible intercellular or intracellular messenger, is known as one of the factors regulating LHRH release in the hypothalamus. Recent study demonstrated that estrogen modulates excitatory amino acid-induced in vitro LHRH release from the arcuate nucleus-median eminence (ARC-ME) fragment in rats. The present study, therefore, was designed to test whether estrogen modulates glutamate-induced in vitro LHRH release by altering NO action and where the action site of NO is. The role of cyclic GMP in mediating NO action was also examined.ARC-ME or ME fragments taken from ovariectomized (OVX) or OVX and estradiol-primed (OVX+E2) rats were incubated in the medium containing glutamate with or without NG-monomethyl-L-arginine (NMMA), a NO synthase inhibitor, or hemoglobin (Hb), a NO scavenger, or in the medium containing sodium nitroprussid (SNP), a NO donor, with or without Hb for 3 min. At the end of the incubation, tissue fragments were homogenized for measurement … More of cGMP contents. In vitro LHRH release from ME fragments taken from both OVX and OVX+E2 rats was significantly increased by incubation with a combination of glutamate and NMMA compared to glutamate treatment alone without changing cGMP contents. NO also seems to have inhibitory effect on glutamate-induced LHRH release in ARC-ME fragments taken from OVX rats as well as in ME fragments. It was further revealed that glutamate increased cGMP level in the ARC-ME fragment taken from OVX rats and the glutamate-induced cGMP increase was blocked by NMMA or Hb. On the other hand, glutamate-induced in vitro LHRH release from ARC-ME fragments taken from OVX+E2 rats was completely suppressed by NMMA or Hb not through the cGMP production. These results clearly demonstrated that estrogen modulates glutamate-induced in vitro LHRH release from the ARC-ME fragment by altering NO tone which mediates the effects of glutamate. On the other hand, NO plays an inhibitory role in mediating glutamate-induced vitro LHRH release from the ME fragment. These results also suggest that NO mediates the action of glutamate on LHRH release in the ARC-ME or ME region in an estrogen-dependent manner, and has a dual role in mediation glutamate-induced LHRH release : one is stimulatory and the other is inhibitory. In addition, NO itself seems to be directly involved in inducing LHRH release from both ARC-ME and ME fragments in the presence of estrogen but not in the absence of estrogen not through cGMP production, since SNP-induced vitro LHRH release from both ARC-ME and ME fragments taken from OVX+E2 rats was block by Hb without changing cGMP contents. In conclusion, the present study suggests that NO mediates the effects of gllutamate on LHRH release at the ARC-ME opr ME region and estrogen alters the effect of NO on LHRH release. NO may, therefore, play an important role in the feedback mechanism of estrogen in the ARC by swithing the inhibitory effect of estrogen to the stimulatory one. Less