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

一氧化氮（NO）是一种新型的细胞内或细胞间扩散性信使，是调节下丘脑LHRH释放的因子之一。最近的研究表明，雌激素调节兴奋性氨基酸诱导的大鼠弓状核-正中隆起（ARC-ME）片段体外释放LHRH。因此，本研究的目的是测试是否雌激素调节谷氨酸诱导的体外LHRH释放通过改变NO的行动和行动的网站是NO。还研究了环GMP在介导NO作用中的作用。将取自卵巢切除（OVX）或OVX和雌二醇致敏（OVX+E2）大鼠的ARC-ME或ME片段在含有或不含谷氨酸的培养基中孵育NO合成酶抑制剂NG-单甲基-L-精氨酸（NMMA）或NO清除剂血红蛋白（Hb），或在含有NO供体硝普钠（SNP）的培养基中，在孵育结束时，将组织碎片均质化用于测量 关于我们 cGMP含量。在体外LHRH释放从ME片段采取OVX和OVX+E2大鼠与谷氨酸和NMMA的组合相比，单独的谷氨酸治疗，而不改变cGMP含量孵育显着增加。NO似乎也有谷氨酸诱导的LHRH释放的抑制作用，从OVX大鼠的ARC-ME片段，以及在ME片段。谷氨酸可使去卵巢大鼠ARC-ME片段中cGMP水平升高，NMMA或Hb可阻断谷氨酸诱导的cGMP升高。另一方面，谷氨酸诱导的体外LHRH释放从ARC-ME片段采取OVX+E2大鼠完全抑制NMMA或血红蛋白不是通过cGMP的生产。这些结果清楚地表明，雌激素调节谷氨酸诱导的体外LHRH释放的ARC-ME片段通过改变NO紧张介导的谷氨酸的影响。另一方面，NO在介导谷氨酸诱导的ME片段的体外LHRH释放中起抑制作用。这些结果也表明，NO介导的作用，谷氨酸对LHRH释放的ARC-ME或ME区域中的雌激素依赖性的方式，并在介导谷氨酸诱导的LHRH释放有双重作用：一个是刺激性的，另一个是抑制性的。此外，NO本身似乎直接参与诱导LHRH释放从ARC-ME和ME片段在雌激素的存在下，但不是在没有雌激素，而不是通过cGMP的生产，因为SNP诱导的体外LHRH释放从ARC-ME和ME片段从OVX+E2大鼠被阻断血红蛋白，而不改变cGMP含量。总之，本研究表明，NO介导谷氨酸对LHRH释放的影响在ARC-ME opr ME区域和雌激素改变NO对LHRH释放的影响。因此，NO可能在雌激素对ARC的反馈机制中起重要作用，使雌激素的抑制作用转变为刺激作用。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