Smith O P Milling, Jabbour H N, Critchley H O D
Department of Reproductive and Developmental Sciences, The University of Edinburgh, Edinburgh, UK.
Hum Reprod. 2007 May;22(5):1450-6. doi: 10.1093/humrep/del503. Epub 2007 Jan 30.
Although the mechanisms underlying the causes of heavy menstrual blood loss (MBL) remain to be elucidated, prostaglandins have been previously implicated. This study was initiated to elucidate a pattern of expression of the various components of the cyclooxygenase (COX)-prostaglandin signalling pathways present in the endometrium of women with normal and heavy MBLs.
Endometrial biopsies were collected at different stages of the menstrual cycle from women who underwent measurement of MBL. Tissue was divided for either examination of gene expression by quantitative RT-PCR analysis or in vitro culture experimentation.
Analysis of gene expression demonstrated a significant elevation in expression of COX-1 and COX-2 mRNA in endometrium obtained from women with heavy MBL when compared with endometrium obtained from women with normal MBL. Tissue culture with PGE(2) stimulation caused a significantly elevated production of cyclic AMP (cAMP) by endometrium of women with heavy MBL when compared with normal MBL. Expression of phosphodiesterase 4B, an enzyme involved in cAMP breakdown, was reduced in these same endometrial samples obtained from women with heavy MBL.
These data identify the E series prostaglandin receptors and their signalling pathways as potential therapeutic targets in the treatment of heavy menstruation.
尽管月经过多(MBL)的潜在病因机制仍有待阐明,但此前已发现前列腺素与之有关。开展本研究旨在阐明环氧化酶(COX)-前列腺素信号通路的各种成分在月经过多和月经正常女性子宫内膜中的表达模式。
从接受MBL测量的女性中,在月经周期的不同阶段采集子宫内膜活检样本。将组织分为两部分,一部分用于通过定量逆转录聚合酶链反应(RT-PCR)分析检测基因表达,另一部分用于体外培养实验。
基因表达分析表明,与月经正常的女性相比,月经过多女性的子宫内膜中COX-1和COX-2 mRNA的表达显著升高。与月经正常的女性相比,用前列腺素E2(PGE2)刺激进行组织培养时,月经过多女性的子宫内膜产生的环磷酸腺苷(cAMP)显著增加。在这些来自月经过多女性的相同子宫内膜样本中,参与cAMP分解的磷酸二酯酶4B的表达降低。
这些数据表明E系列前列腺素受体及其信号通路是治疗月经过多的潜在治疗靶点。