Huang Jaou-Chen, Arbab Farinaz, Tumbusch Katherine J, Goldsby Jennifer S, Matijevic-Aleksic Nena, Wu Kenneth K
Department of Obstetrics and Gynecology, University of Texas Medical School at Houston, Institute of Molecular Medicine and Division of Hematology, Texas 77030, USA.
J Clin Endocrinol Metab. 2002 Sep;87(9):4361-8. doi: 10.1210/jc.2002-020199.
Animal studies unequivocally support the indispensable role of prostaglandin (PG) and cyclooxygenase (COX) in ovulation and implantation. Available data also suggest that PG and COX may be important in the transport of embryos. The effects of PGE(2) and PGF(2alpha) on the contractility of human tubal muscle have been studied extensively; the expression of COX in human fallopian tubes was also reported. Despite all these, two fundamentally important questions remained to be answered: 1) which PGs are produced by human fallopian tubes; and 2) which COX isoform(s) is expressed by the fallopian tubes. We used reverse-phase HPLC to study the metabolism of [1-(14)C] arachidonic acid by the fallopian tubes. We found that 6 keto-PGF(1alpha), a stable metabolite of prostacyclin (PGI), and PGE(2) constituted 56% +/- 10% and 35% +/- 10% (mean +/- SEM, four samples), respectively, of total eicosanoids synthesized. Western blot analysis revealed the expression of both COX isoforms. Immunohistochemistry study showed that both COX-1 and -2 were localized to nonciliated epithelia and tubal smooth muscle. In addition, COX-2 was also expressed in ciliated epithelial cells. Western blot analysis revealed the expression of PGI synthase (PGIS) and PGI receptor by fallopian tubes. Immunohistochemistry confirmed the expression of PGIS by luminal epithelia, tubal smooth muscle, vascular endothelial cells, and vascular smooth muscle cells. Iloprost, a PGI analog, inhibited the activities of circular and longitudinal muscles of the fallopian tube. Thus, the fallopian tube expresses both COX isoforms and PGIS. Furthermore, it is a source and a target of PGI. PGI and COX may be important to gamete function, embryo transport, and embryo development.
动物研究明确支持前列腺素(PG)和环氧化酶(COX)在排卵和着床过程中不可或缺的作用。现有数据还表明,PG和COX在胚胎运输中可能也很重要。人们已经广泛研究了PGE(2)和PGF(2α)对人输卵管肌肉收缩性的影响;也有关于COX在人输卵管中表达的报道。尽管如此,仍有两个至关重要的问题有待解答:1)人输卵管产生哪些PG;2)输卵管表达哪种COX同工型。我们使用反相高效液相色谱法研究输卵管对[1-(14)C]花生四烯酸的代谢。我们发现,前列环素(PGI)的稳定代谢产物6-酮-PGF(1α)和PGE(2)分别占合成的总类二十烷酸的56%±10%和35%±10%(平均值±标准误,四个样本)。蛋白质印迹分析显示两种COX同工型均有表达。免疫组织化学研究表明,COX-1和-2均定位于非纤毛上皮和输卵管平滑肌。此外,COX-2在纤毛上皮细胞中也有表达。蛋白质印迹分析显示输卵管表达PGI合酶(PGIS)和PGI受体。免疫组织化学证实管腔上皮、输卵管平滑肌、血管内皮细胞和血管平滑肌细胞均表达PGIS。PGI类似物伊洛前列素抑制输卵管环形和纵形肌肉的活性。因此,输卵管表达两种COX同工型和PGIS。此外,它是PGI的来源和靶点。PGI和COX可能对配子功能、胚胎运输和胚胎发育很重要。