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

女性中一氧化氮对黄体生成素释放激素释放的中枢调节。

• 批准号: 06454125
• 负责人: MAEDA Kei-ichiro
• 金额: $ 3.78万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454125/
• 关键词: luteinizing hormone-releasing hormone; nitric oxide; arcuate nucleus; median eminence; excitatory amino acid; rat; エストロジェン; サイクリックGMP; 一酸化窒素(NO)

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

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释放的因素之一。最近的研究表明，雌激素调节兴奋性氨基酸诱导的大鼠弓形核-中位隆起（ARC-ME）片段的体外LHRH释放。因此，本研究旨在检测雌激素是否通过改变NO的作用以及NO的作用部位来调节谷氨酸诱导的体外LHRH释放。并探讨了环GMP介导NO的作用。从卵巢切除（OVX）或OVX和雌二醇启动（OVX+E2）大鼠中提取的ARC-ME或ME片段在含谷氨酸(含或不含ng -单甲基- l-精氨酸（NMMA）， NO合成酶抑制剂，或血红蛋白（Hb）， NO清除剂，或含硝普钠（SNP）， NO供体，含或不含Hb的培养基中孵育3分钟。孵育结束后，将组织碎片匀浆以测定cGMP含量。与谷氨酸单独处理相比，谷氨酸和NMMA联合孵育后，OVX和OVX+E2大鼠ME片段的体外LHRH释放量显著增加，而cGMP含量未发生变化。NO似乎也对OVX大鼠ARC-ME片段和ME片段中谷氨酸诱导的LHRH释放有抑制作用。进一步发现谷氨酸增加了OVX大鼠ARC-ME片段的cGMP水平，并且谷氨酸诱导的cGMP增加被NMMA或Hb阻断。另一方面，谷氨酸诱导的OVX+E2大鼠ARC-ME片段体外LHRH释放被NMMA或Hb完全抑制，而不是通过cGMP产生。这些结果清楚地表明，雌激素通过改变介导谷氨酸作用的NO音调，调节谷氨酸诱导的体外LHRH从ARC-ME片段释放。另一方面，NO在谷氨酸诱导的体外LHRH从ME片段释放中起抑制作用。这些结果也提示NO以雌激素依赖的方式介导谷氨酸对ARC-ME或ME区LHRH释放的作用，在谷氨酸诱导的LHRH释放中具有刺激和抑制双重作用。此外，NO本身似乎直接参与在雌激素存在的情况下诱导ARC-ME和ME片段释放LHRH，而在没有雌激素的情况下不通过cGMP产生，因为从OVX+E2大鼠中提取的ARC-ME和ME片段的snp诱导的体外LHRH释放被Hb阻断，而不改变cGMP含量。综上所述，本研究提示NO介导谷氨酸在ARC-ME或ME区对LHRH释放的影响，雌激素改变NO对LHRH释放的影响。因此，NO可能在ARC中雌激素的反馈机制中发挥重要作用，将雌激素的抑制作用转变为刺激作用。少

项目成果

Murahashi,Kumiko: "Suppression of LH pulses by restriction of glucose availability is mediated by sensors in the brain stem." Endocrinology. 137(印刷中). (1996)

Murahashi, Kumiko：“通过限制葡萄糖可用性来抑制 LH 脉冲是由脑干中的传感器介导的。”137（出版中）。

Solis, C.D., Kawamoto, Y., Tanaka, K., Masangkay, J.S., Maeda, K.-I.and Namikawa, T.: "The Tamaraw (Bubalus (B.) mindorensis) hemologlobin phenotipe and comparison among the Asian buffaloes based on isoelectric focusing." Aminal Science and Technology (Jp

Solis, C.D.、Kawamoto, Y.、Tanaka, K.、Masangkay, J.S.、Maeda, K.-I. 和 Namikawa, T.：“Tamaraw (Bubalus (B.) Mindorensis) 血红蛋白表型和亚洲水牛之间的比较

Maeda,Kei-ichiro: "Involvement of catecholaminergic input to the paraventricular nucleus and of corticotropin-releasing homone in the fasting-induced suppression of luteinizing hormone release in female rats." Endocrinology. 134. 1718-1722 (1994)

Maeda，Kei-ichiro：“室旁核的儿茶酚胺能输入和促肾上腺皮质激素释放激素参与雌性大鼠禁食诱导的黄体生成激素释放的抑制。”

Murahashi,Kumiko: "Suppression of LH pulses by restriction of glucose availability is mediated by sensors in the brain stem." Endocrinology. 137,(印刷中). (1996)

Murahashi, Kumiko：“通过限制葡萄糖可用性来抑制 LH 脉冲是由脑干中的传感器介导的。”（1996 年出版）。

Maeda,Kei-ichiro: "Novel estrogen feedback sites associated with stress-induced suppression of luteinizing hormone secretion in female rats." Celler and Molecular Neurobiology. (印刷中). (1996)

Maeda, Kei-ichiro：“与应激诱导的雌性大鼠黄体生成素分泌抑制相关的新雌激素反馈位点。” Celler 和分子神经生物学（1996 年出版）。