Estrogen and progesterone metabolism in the cervix during pregnancy and parturition
Estrogen and progesterone metabolism in the cervix during pregnancy and parturition
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DOI：
10.1210/jc.2007-2813
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发表时间：
2008-06-01
影响因子：
5.8
通讯作者：
Word, R. Ann
中科院分区：
文献类型：
--
作者：
Andersson, Stefan;Minjarez, Debra;Word, R. Ann
背景：在各种非灵长类动物中的实验和临床研究表明，黄体酮的退出会导致基因表达的变化，从而在足月开始分娩。5α-还原酶I型缺陷小鼠未能在足月子宫颈成熟，尽管黄体溶解和黄体酮在血液中及时停止。目的：我们的目的是验证怀孕期间宫颈组织中雌激素和孕酮代谢受到调节的假说，即使在分娩不以血液中孕酮退出为特征的物种中也是如此。设计：对足月未怀孕和怀孕妇女在分娩前或分娩后的完整宫颈组织中雌二醇和孕酮代谢进行定量。背景：研究在一所大学医院进行。患者：组织取自5名未怀孕和21名孕妇(9名临产前和12名分娩中)。主要观察指标：酶活性测量，采用Northern印迹分析、实时定量RT-PCR和免疫组织化学方法对宫颈和子宫肌层组织中的类固醇激素代谢酶进行定量。结果：妊娠期腺上皮细胞表达17β-羟基类固醇脱氢酶2，催化雌二醇转化为雌酮，间质来源的20α-羟孕酮转化为孕酮。在分娩过程中，宫颈内细胞中17β-羟基类固醇脱氢酶2表达下调，从而创造了一个有利于宫颈成熟的微环境。结论：这些数据表明，分娩期间宫颈成熟通过宫颈上皮和间质之间的复杂关系对雌激素和孕酮代谢进行局部调节，妊娠妇女宫颈组织中的类固醇激素代谢是不同于小鼠的。
Context: Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes in gene expression that initiate parturition at term. Mice deficient in 5 alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood.Objective: Our objective was to test the hypothesis that estrogen and progesterone metabolism is regulated in cervical tissues during pregnancy, even in species in which parturition is not characterized by progesterone withdrawal in blood.Design: Estradiol and progesterone metabolism was quantified in intact cervical tissues from nonpregnant and pregnant women at term before or after labor.Setting: The study was conducted at a university hospital.Patients: Tissues were obtained from five nonpregnant and 21 pregnant women (nine before labor and 12 in labor).Main Outcome Measures: Enzyme activity measurements, Northern blot analysis, quantitative real-time RT-PCR, and immunohistochemistry were used to quantify steroid hormone metabolizing enzymes in cervical and myometrial tissues.Results: During pregnancy, 17 beta-hydroxysteroid dehydrogenase type 2 was induced in glandular epithelial cells to catalyze the conversion of estradiol to estrone and stroma-derived 20 alpha-hydroxyprogesterone to progesterone. During parturition, 17 beta-hydroxysteroid dehydrogenase type 2 was down-regulated in endocervical cells, thereby creating a microenvironment favorable for cervical ripening.Conclusions: Together, the data indicate that cervical ripening during parturition involves localized regulation of estrogen and progesterone metabolism through a complex relationship between cervical epithelium and stroma, and that steroid hormone metabolism in cervical tissues from pregnant women is unique from that in mice.