Regulation of human aromatase cytochrome P450 gene expression
Regulation of human aromatase cytochrome P450 gene expression
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DOI：
10.1016/0960-0760(92)90320-i
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发表时间：
1992-12
期刊：
影响因子：
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通讯作者：
E. Simpson;M. Kilgore;M. Mahendroo;G. Means;C. Corbin;C. Mendelson
中科院分区：
文献类型：
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作者：
E. Simpson;M. Kilgore;M. Mahendroo;G. Means;C. Corbin;C. Mendelson
在人类中，雌激素生物合成发生在几个组织部位，包括卵巢、胎盘、脂肪和脑。我们实验室最近的工作表明，芳香化酶细胞色素P450（P450 arom），负责雌激素生物合成的酶的组织特异性表达，是确定的，在一定程度上，通过使用组织特异性启动子。因此，P450 arom在人卵巢中的表达似乎利用了邻近翻译起始位点的启动子。该启动子不用于胎盘，而是用于驱动胎盘中芳香酶表达的启动子位于翻译起始位点上游至少40 kb处。此外，在小部分胎盘转录物的表达中使用了一个次要启动子，其位于翻译起始点上游9 kb处。来自这些启动子的转录物也在其他胎儿组织中表达，包括胎盘相关细胞如JEG-3脉络膜癌细胞、葡萄胎和其他胎儿组织如胎儿肝脏。另一方面，在脂肪组织中，P450 arom的表达可以通过另一种脂肪特异性启动子来实现。由这些启动子驱动的表达所特有的各种5′-非翻译外显子被剪接到翻译起始位点上游的共同内含子/外显子边界中。这意味着在雌激素生物合成的各个组织特异性位点中表达的蛋白质是相同的。
In the human, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory has indicated that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start-site. This promoter is not utilized in placenta but instead, the promoter used to drive aromatase expression in placenta is at least 40 kb upstream from the translational start-site. In addition, there is a minor promoter used in the expression of a small proportion of placental transcripts which is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues including placenta-related cells such as JEG-3 choricarcinoma cells, hydatidiform moles, and other fetal tissues such as fetal liver. On the other hand, in adipose tissue expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5′-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start-site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical.