The Human Placenta Expresses CYP17 and Generates Androgens De Novo
The Human Placenta Expresses CYP17 and Generates Androgens De Novo
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DOI：
10.1210/jc.2010-2504
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发表时间：
2011-05-01
影响因子：
5.8
通讯作者：
Carr, B. R.
中科院分区：
文献类型：
--
作者：
Escobar, J. C.;Patel, S. S.;Carr, B. R.
简介：人胎盘中CYP 17的表达被认为是不显著的，这使得它依赖于母体和胎儿的室来获得必要的雄激素前体，以产生妊娠中所见的高水平的雌激素。目的：本研究的目的是分析人滋养层细胞是否能够表达CYP 17并重新产生雄激素。来自新鲜胎盘的人滋养层细胞和JEG-3细胞用于所有实验。通过RT-PCR进行CYP 17 mRNA分析，通过Western blot和免疫组织化学染色进行蛋白质检测。结果：CYP 17 mRNA在两种细胞中均有表达。CYP 17蛋白通过Western blotting检测，并通过免疫染色主要定位于合胞体滋养细胞的细胞质。17 α-羟孕酮，雄烯二酮，和它们的芳香化产物在培养基中的测量进一步证明了CYP 17在人滋养层中的表达和活性。CYP 17类固醇产品的基线水平较高的原代细胞和显着增加的存在下，22-hydroxycholesterol.Conclusions：我们已经证明了CYP 17 mRNA和蛋白质的表达和活性在人类滋养层细胞。考虑到胎盘的前体浓度、血流量和质量，我们认为它对雄激素的贡献是妊娠期雌激素产生的重要来源。（临床内分泌代谢杂志96：1385-1392，2011）
Introduction: The human placenta is believed to have insignificant CYP17 expression, rendering it dependent on the maternal and fetal compartments for the necessary androgenic precursors to yield the high levels of estrogens seen in pregnancy.Objective: The aim of the study was to analyze whether the human trophoblast is capable of expressing CYP17 and producing androgens de novo.Methods: Human trophoblasts from fresh placentas and JEG-3 cells were used for all experiments. CYP17 mRNA analysis was performed via RT-PCR, and protein detection by Western blot and immunohistochemical staining. Steroid products were quantified using RIAs.Results: CYP17 mRNA was expressed in both cell types. CYP17 protein was detected by Western blotting and localized by immunostaining mainly to the cytoplasm of syncytiotrophoblasts. Measurement of 17 alpha-hydroxyprogesterone, androstenedione, and their aromatized products in the media further demonstrated CYP17 expression and activity in the human trophoblast. Baseline levels of CYP17 steroid products were higher in primary cells and significantly increased in the presence of 22-hydroxycholesterol.Conclusions: We have demonstrated CYP17 mRNA and protein expression and activity in human trophoblasts. Considering the precursor concentration, blood flow, and mass of the placenta, we suggest that its contribution of androgens is an important source of estrogen production in pregnancy. (J Clin Endocrinol Metab 96: 1385-1392, 2011)