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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Role of nitric oxide in control of prolactin release by the adenohypophysis.
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Role of nitric oxide in control of prolactin release by the adenohypophysis.

机译:一氧化氮在腺垂体控制泌乳素释放中的作用。

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摘要

Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 microM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the prolactin-releasing action of vasoactive intestinal polypeptide and substance P, but mediates the prolactin-inhibiting activity ofdopamine and atrial natriuretic factor.
机译:通过免疫细胞化学观察到垂体前叶中含有一氧化氮合酶的细胞。因此,我们开始评估NO在控制垂体前叶功能中的可能作用。催乳素通常处于抑制性下丘脑控制下,在体外腺体会分泌大量激素。将半垂体在硝普钠(一种NO的释放剂)存在下孵育30分钟后,其催乳素释放受到抑制。这种抑制作用被NO血红蛋白清除剂完全阻断。精氨酸的类似物(例如NG-单甲基-L-精氨酸(NMMA,其中NG是胍基氮的末端)和硝基精氨酸甲酯)可抑制NO合酶。将半垂体与这些化合物中的任一个一起孵育显着增加了催乳素的释放。由于在其他组织中,大多数NO的作用都由可溶性鸟苷酸环化酶的激活与环状GMP的形成介导,因此我们评估了环状GMP对催乳素释放的影响。循环GMP(10 mM)使催乳素释放减少了约40%。催乳素在体内和体外的释放可以被包括血管活性肠多肽和P物质在内的几种肽刺激。因此,我们通过在这些肽单独存在或在其中存在下孵育腺体,评估了NO在这些刺激中的可能作用。与NMMA结合使用。对于具有血管活性的肠多肽,NMMA增强了催乳素释放的显着刺激,从而产生了累加作用。对于P物质,催乳激素的释放量较小但明显,而NMMA并未显着增加。我们得出结论,NO对这两种肽对催乳素释放的刺激作用几乎没有影响。多巴胺(0.1 microM)是催乳激素释放的抑制剂,可减少催乳激素的释放,这种抑制作用被血红蛋白(20微克/ ml)或NMMA显着阻断,并被1 mM硝基精氨酸甲酯完全阻断。 1 microM的心钠素也减少了催乳素的释放,其作用被NMMA完全阻断。与催乳素的这些结果相反,在测试硝普钠对催乳素释放有影响的同一培养基中测量了黄体生成素(LH),硝普钠,血红蛋白或硝普钠和血红蛋白的组合对促黄体生成激素没有影响释放。因此,与其对催乳激素释放的抑制作用相反,NO对促黄体生成激素的释放没有影响。其他人的免疫细胞化学研究表明,卵泡状细胞以及垂体的促性腺激素中不存在合酶。我们得出的结论是,这两种细胞类型产生的NO都可能扩散到促乳素,从而抑制催乳素的释放。 NO在血管活性肠多肽和P物质的催乳激素释放作用中似乎没有什么作用,但介导了多巴胺和心钠素的催乳素抑制活性。

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