Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics/Gynecology, The University of Texas Southwestern Medical Center, Dallas, TX 75235-9051, USA.
J Steroid Biochem Mol Biol. 1992 Dec;43(8):923-30. doi: 10.1016/0960-0760(92)90320-I.
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.
在人体中，雌激素生物合成发生在多个组织部位，包括卵巢、胎盘、脂肪组织和大脑。我们实验室的最新研究表明，芳香化酶细胞色素 P450（P450arom）的组织特异性表达，负责雌激素生物合成的酶，部分取决于组织特异性启动子的使用。因此，人卵巢中 P450arom 的表达似乎利用了靠近翻译起始位点的启动子。该启动子在胎盘组织中不被利用，相反，用于驱动胎盘组织中芳香酶表达的启动子至少位于翻译起始位点上游 40kb。此外，还有一个次要的启动子用于表达一小部分胎盘转录本，该启动子位于翻译起始位点上游 9kb。这些启动子的转录本也在其他胎儿组织中表达，包括胎盘相关细胞，如 JEG-3 绒毛膜癌细胞、葡萄胎和其他胎儿组织，如胎肝。另一方面，脂肪组织中 P450arom 的表达可能是通过另一个脂肪组织特异性启动子实现的。由每个启动子驱动表达的各种 5'非翻译外显子都被剪接到翻译起始位点上游的一个共同内含子/外显子边界处。这意味着在雌激素生物合成的各种组织特异性部位表达的蛋白质是相同的。
