Mechanisms in the regulation of aromatase in developing ovary and placenta
Mechanisms in the regulation of aromatase in developing ovary and placenta
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DOI：
10.1016/j.jsbmb.2007.05.001
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发表时间：
2007-08-01
影响因子：
4.1
通讯作者：
Kamat, Amrita
中科院分区：
文献类型：
--
作者：
Mendelson, Carole R.;Kamat, Amrita
在人类妊娠期间，胎盘的合体滋养细胞发育出了从胎儿肾上腺分泌的c -19类固醇合成大量雌激素的能力。c -19甾体的转化；芳香化酶P450 （P450arom）是CYP19基因的产物。hCYP19基因的胎盘特异性启动子位于II外显子翻译起始位点上游100,000 bp处。在使用转基因小鼠和转染的人滋养细胞的研究中，我们在胎盘特异性外显子L I上游定义了一个246 bp的区域，该区域介导胎盘细胞特异性表达。在转基因小鼠中，我们还观察到卵巢特异性hCYP19外显子Ha 5'端侧278 bp的DNA足以靶向卵巢特异性表达。这种卵巢特异性启动子含有结合cAMP-response element-binding protein （CREB）和孤儿核受体SF-1和LRH- 1的应答元件，它们是在发情周期和妊娠期间camp介导的颗粒细胞和黄体细胞中CYP19表达的刺激所必需的。在本文中，我们回顾了我们的研究，以确定基因组区域和应答元件介导胎盘特异性表达的hCYP19基因。LRH- 1与SF-1在小鼠胚胎发育性腺和产后卵巢中的时空表达也将被考虑。(C) 2007 Elsevier Ltd.版权所有。
During human gestation, the placental syncytiotrophoblast develops the capacity to synthesize large amounts of estrogen from C-19-steroids secreted by the fetal adrenals. The conversion of C-19-steroids; to estrogens is catalyzed by aromatase P450 (P450arom), product of the CYP19 gene. The placenta- specific promoter of the hCYP19 gene lies similar to 100,000 bp upstream of the translation initiation site in exon II. In studies using transgenic mice and transfected human trophoblast cells we have defined a 246-bp region upstream of placenta-specific exon L I that mediates placental cell-specific expression. Using transgenic mice, we also observed that as little as 278 bp of DNA flanking the 5'-end of ovary-specific hCYP19 exon Ha was sufficient to target ovary-specific expression. This ovary-specific promoter contains response elements that bind cAMP-response element-binding protein (CREB) and the orphan nuclear receptors SF-1 and LRH- 1, which are required for cAMP-mediated stimulation of CYP19 expression in granulosa and luteal cells during the estrous cycle and pregnancy. In this article, we review our studies to define genomic regions and response elements that mediate placenta-specific expression of the hCYP19 gene. The temporal and spatial expression of LRH- 1 versus SF-1 in the developing gonad during mouse embryogenesis and in the postnatal ovary also will be considered. (C) 2007 Elsevier Ltd. All rights reserved.