Giannoulias D, Alfaidy N, Holloway A C, Gibb W, Sun M, Lye S J, Challis J R G
Canadian Institutes of Health Research in Human Development, Department of Physiology, University of Toronto, 1 King's College Circle, Medical Sciences Building Room 3344, Toronto, Ontario, Canada M5S 1A8.
J Clin Endocrinol Metab. 2002 Nov;87(11):5274-82. doi: 10.1210/jc.2002-020521.
Prostaglandins (PGs) act as potent uterotonins at the time of labor. Prostaglandin E synthase (PGES) is responsible for the formation of PGE(2), a uterotonin. PGI(2) is synthesized by the prostaglandin I synthase enzyme (PGIS) and contributes to relaxation in the lower uterine segment. We examined the expression of membrane-bound PGES and PGIS in myometrium from pregnant women during preterm and term labor. Tissues were collected from the lower uterine segment from preterm no labor, preterm labor, term no labor, and term labor patients and used for immunohistochemistry and Western blot analysis using specific antibodies. Immunoreactive (ir-) PGES and PGIS proteins were localized to the cytoplasm of myocytes of the myometrium and vascular smooth muscle cells. Ir-PGES was also detected in vascular endothelial cells. Western blot analyses revealed a predominant protein band of 180 kDa, and a second 16-kDa band for ir-PGES and 56-kDa band for ir-PGIS. There was no significant change in ir-PGES protein (180 or 16 kDa) or mRNA levels with preterm or term labor or gestational age. There was a significant decrease in PGIS mRNA and protein with advancing gestational age. We conclude that the gestational age decrease in the inhibitory PGIS is consistent with lessening of its influence in myometrium at the time of labor. The lack of change in PGES indicates that alterations at other points along the pathway of arachidonic acid metabolism may be of greater importance in affecting local changes in PGE(2).
前列腺素(PGs)在分娩时作为强效子宫收缩剂起作用。前列腺素E合酶(PGES)负责生成PGE₂,一种子宫收缩剂。前列环素(PGI₂)由前列腺素I合酶(PGIS)合成,并有助于子宫下段松弛。我们研究了早产和足月分娩孕妇子宫肌层中膜结合型PGES和PGIS的表达。从早产未临产、早产临产、足月未临产和足月临产患者的子宫下段采集组织,并用特异性抗体进行免疫组织化学和蛋白质印迹分析。免疫反应性(ir-)PGES和PGIS蛋白定位于子宫肌层肌细胞和血管平滑肌细胞的细胞质中。在血管内皮细胞中也检测到ir-PGES。蛋白质印迹分析显示,ir-PGES的主要蛋白条带为180 kDa,第二条为16 kDa,ir-PGIS为56 kDa。早产或足月分娩以及孕周对ir-PGES蛋白(180或16 kDa)或mRNA水平均无显著影响。随着孕周增加,PGIS的mRNA和蛋白水平显著降低。我们得出结论,抑制性PGIS随孕周的减少与分娩时其对子宫肌层影响的减弱一致。PGES缺乏变化表明,花生四烯酸代谢途径其他点的改变可能在影响PGE₂的局部变化方面更为重要。