Ahmed A, Cameron I T, Ferriani R A, Smith S K
Department of Obstetrics and Gynaecology, University of Cambridge, U.K.
J Endocrinol. 1992 Nov;135(2):383-90. doi: 10.1677/joe.0.1350383.
Human endometrium contains specific binding sites for iodinated endothelin (ET)-1, ET-2 and ET-3, and ET-1 stimulates prostaglandin (PG) F2 alpha synthesis from explants of proliferative endometrium in short-term culture. This study has investigated the cellular responses of normal proliferative endometrium to ET-1. Radioimmunoassay was used to measure PG release and Dowex anion-exchange column chromatography was utilized to assess the accumulation of inositol phosphates. Endothelin-1 induced a significant increase in PGF2 alpha release (basal median: 1465 pg/mg per 60 min (range: 541-3935 pg/mg per 60 min); ET-1-stimulated: 1813 pg/mg per 60 min (1021-5714 pg/mg per 60 min); P < 0.04 using Wilcoxon signed rank test). The effect of ET-1 was attenuated in the presence of the phospholipase A2 inhibitor quinacrine. Endothelin-1 induced a rapid, transient and concentration-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), measured by the accumulation of tritiated inositol phosphates. Following a 1-min stimulation with ET-1 (100 nmol/l), [3H]inositol mono-, bis- and trisphosphate fractions increased from median values of 490.0 d.p.m./mg dry wt (range: 348.0-807.0 d.p.m./mg dry wt), 120.0 d.p.m./mg dry wt (93.6-144.1 d.p.m./mg dry wt) and 67.0 d.p.m./mg dry wt (54.2-85.0 d.p.m./mg dry wt) to 939.0 d.p.m./mg dry wt (635.9-1596.0 d.p.m./mg dry wt; P < 0.03), 145.0 d.p.m./mg dry wt (127.0-293.9 d.p.m./mg dry wt; P < 0.05) and 146.0 d.p.m./mg dry wt (77.5-187.0 d.p.m./mg dry wt; P < 0.03) respectively. These results suggest that ET-1 activates the phospholipase A2 and PtdIns(4,5)P2-specific phospholipase C in human proliferative endometrium, resulting in the generation of PGF2 alpha and second messengers respectively which are pivotal to endometrial function.
人子宫内膜含有碘化内皮素（ET）-1、ET-2和ET-3的特异性结合位点，并且ET-1在短期培养中可刺激增殖期子宫内膜外植体合成前列腺素（PG）F2α。本研究调查了正常增殖期子宫内膜对ET-1的细胞反应。采用放射免疫分析法测定PG释放量，并利用Dowex阴离子交换柱色谱法评估肌醇磷酸的积累情况。内皮素-1可显著增加PGF2α的释放（基础中位数：每60分钟1465 pg/mg（范围：每60分钟541 - 3935 pg/mg）；ET-1刺激后：每60分钟1813 pg/mg（1021 - 5714 pg/mg每60分钟）；使用Wilcoxon符号秩检验，P < 0.04）。在磷脂酶A2抑制剂奎纳克林存在的情况下，ET-1的作用减弱。内皮素-1可诱导磷脂酰肌醇4,5 - 二磷酸（PtdIns(4,5)P2）快速、短暂且浓度依赖性的水解，这通过氚标记的肌醇磷酸的积累来测定。用ET-1（100 nmol/l）刺激1分钟后，[3H]肌醇单磷酸、双磷酸和三磷酸部分分别从中位数490.0 d.p.m./mg干重（范围：348.0 - 807.0 d.p.m./mg干重）、120.0 d.p.m./mg干重（93.6 - 144.1 d.p.m./mg干重）和67.0 d.p.m./mg干重（54.2 - 85.0 d.p.m./mg干重）增加到939.0 d.p.m./mg干重（635.9 - 1596.0 d.p.m./mg干重；P < 0.03）、145.0 d.p.m./mg干重（127.0 - 293.9 d.p.m./mg干重；P < 0.05）和146.0 d.p.m./mg干重（77.5 - 187.0 d.p.m./mg干重；P < 0.03）。这些结果表明，ET-1激活人增殖期子宫内膜中的磷脂酶A2和PtdIns(4,5)P2特异性磷脂酶C，分别导致PGF2α和第二信使的产生，而它们对于子宫内膜功能至关重要。
