A possible role for lipoxygenase and epoxygenase arachidonate metabolites in prolactin release from pituitary cells.
A possible role for lipoxygenase and epoxygenase arachidonate metabolites in prolactin release from pituitary cells.
复制标题
脂氧合酶和环氧化酶花生四烯酸代谢物在垂体细胞释放催乳素中的可能作用。
DOI：
10.1159/000125042
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发表时间：
1988
影响因子：
4.1
通讯作者：
MacLeod,RM
中科院分区：
文献类型：
--
作者：
Judd,AM;Spangelo,BL;Ehreth,JT;MacLeod,RM
本实验研究了选定的白三烯和羟基二碳四烯酸（HETEs）对雌性大鼠垂体前叶细胞原代培养中泌乳素释放的影响。白三烯B4、C4和D4对泌乳素基础释放无影响；然而，它们确实增加了1或5纳米促甲状腺素释放激素（TRH）刺激的催乳素释放。白三烯C4还能增强肉豆蔻酸佛波酯（一种蛋白激酶C激活剂）、乳酸菌毒素（一种钙摄取刺激剂）和血管紧张素II诱导的催乳素释放。5-HETE、12-HETE和15-HETE在高浓度（1 μ m以上）刺激基础催乳素释放，5-HETE和12-HETE在较低（纳摩尔）浓度下也促进trh和血管紧张素ii诱导的催乳素释放。为了确定内源性花生四烯酸代谢物在催乳素释放中的作用，将垂体细胞培养暴露于选定的5-脂氧合酶抑制剂（将花生四烯酸代谢为白三烯和5-HETE）和环氧化酶抑制剂（将花生四烯酸代谢为环氧二十碳三烯酸）中。这些抑制剂减少了基础和分泌激素诱导的催乳素释放。在另外的实验中，通过高效液相色谱分析，我们发现TRH可以促进花生四烯酸代谢物从垂体细胞中释放，类似于白三烯c4和ω- oh -白三烯B4（白三烯B4的代谢物）和HETEs。因此，白三烯、HETEs和环氧二碳三烯酸的产生可能是催乳素正常释放所必需的。
We studied the effects of selected leukotrienes and hydroxyeicosatetraenoic acids (HETEs) on prolactin release from primary cultures of female rat anterior pituitary cells. Leukotrienes B4, C4, and D4 had no effect on basal prolactin release; however, they did enhance prolactin release that was stimulated by 1 or 5 nMthyrotropin-releasing hormone (TRH). Leukotriene C4 also enhanced prolactin release that was induced by phorbol myristate acetate (a protein kinase C activator) by maitotoxin (a calcium uptake stimulator), and by angiotensin II. 5-HETE, 12-HETE, and 15-HETE stimulated basal prolactin release at high concentrations (1 µMand greater), and 5-HETE and 12-HETE enhanced TRH-and angiotensin II-induced prolactin release at lower (nanomolar) concentrations as well. In order to determine the role of endogenous arachidonate metabolites in prolactin release, pituitary cell cultures were exposed to selected inhibitors of the 5-lipoxygenase enzyme, which metabolizes arachidonate to leukotrienes and 5-HETE, and to those of the epoxygenase enzyme, which metabolizes arachidonate to epoxyeicosatrienoic acids. These inhibitors decreased basal and secretagogue-induced prolactin release. In additional experiments, it was determined that TRH enhances the liberation from pituitary cells of arachidonate metabolites with high-performance liquid chromatography elution profiles similar to those of leukotriene C4and ω-OH-leukotriene B4 (a metabolite of leukotriene B4) and the HETEs. Therefore, the production of leukotrienes, HETEs, and epoxyeicosatrienoic acids may be necessary for the normal release of prolactin.