Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy
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DOI:
10.1186/1477-7827-5-30
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发表时间:
2007-07-10
影响因子:
4.4
通讯作者:
Tremblay, Yves
Tremblay, Yves
中科院分区:
医学2区
文献类型:
--
作者:
Drolet, Renee;Simard, Marc;Tremblay, Yves

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背景:在人类妊娠期间,胎盘绒毛产生大量的雌二醇。这种类固醇由合胞体分泌,合胞体直接与母体血液接触。胎盘必须穿过胎盘和胎儿血管才能到达胎儿循环系统。在绒毛内胎儿血管的胎盘内皮细胞中检测到17 β-羟基类固醇脱氢酶2型(17 β-HSD 2)。这种酶催化雌二醇转化为雌酮,睾酮转化为雄烯二酮。17 β-HSD 2可能调控进入胎儿循环的雌二醇水平。方法:收集自愿终止妊娠妇女孕10 ~ 26 6/ 7周的胎盘,正常自然阴道分娩的足月胎盘。我们通过RT-QPCR定量了妊娠中期和足月人胎盘中的17 β-HSD 2 mRNA水平。我们制备了一种新的抗17 β-HSD 2抗体,通过免疫组织化学研究其时空表达。我们还比较了激素水平(睾酮,雌酮和雌二醇)和17 β-HSD 2 mRNA和蛋白水平之间的足月胎盘和子宫内膜。结果:高17 β-HSD 2 mRNA和蛋白水平被发现在中期妊娠和足月胎盘。然而,我们发现17 β-HSD 2 mRNA水平在妊娠中期和足月之间增加了2.27倍。这一时期与绒毛血管系统发育的过渡阶段相吻合。在妊娠中期的胎盘中,在间充质绒毛和未成熟的中间绒毛中发现了高水平的17 β-HSD 2,更准确地说是在基质通道的内皮细胞中。足月时,在终末绒毛的众多窦状毛细血管中发现高水平的17 β-HSD 2。足月胎盘中17 β-HSD 2 mRNA和蛋白水平分别是子宫内膜的25.4倍和30 - 60倍。类固醇水平也显着高于足月胎盘比在子宫内膜。结论:17 β-HSD 2的空间和时间的表达,在妊娠期间的胎盘和胎盘绒毛和子宫内膜之间的17 β-HSD 2的表达和类固醇水平的比较是兼容的作用,在调制的活性和非活性形式的雌激素。我们的观察结果强烈支持这一假设,即17 β-HSD 2作为一个障碍,降低雌二醇分泌率在胎儿循环。
Background: During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2.Methods: We obtained placentas from 10 to 26 6/ 7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti- 17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol) and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium.Results: High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium.Conclusion: The spatial and temporal expression of 17beta-HSD2 in the placenta during pregnancy and the comparison of 17beta-HSD2 expression and steroid levels between placental villi and endometrium are compatible with a role in the modulation of active and inactive forms of estrogens. Our observations strongly support the hypothesis that 17beta-HSD2 acts as a barrier decreasing estradiol secretion rates in the foetal circulation.