Hakkola J, Raunio H, Purkunen R, Pelkonen O, Saarikoski S, Cresteil T, Pasanen M
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Biochem Pharmacol. 1996 Jul 26;52(2):379-83. doi: 10.1016/0006-2952(96)00216-x.
Human first-trimester placentas were screened for the expression of xenobiotic-metabolizing cytochrome P450 (CYP) genes. mRNAs of CYP1A1, CYP1A2, CYP2C, CYP2D6, CYP2E1, CYP2F1, CYP3A4, CYP3A5, CYP3A7, and CYP4B1 were identified by reverse transcriptase-polymearse chain reaction (RT-PCR) in at least some of the six placental samples studied. CYP2A and CYP2B message were absent in all samples. The level of all of these CYP mRNAs was lower compared to the corresponding levels in liver or lung. the catalytic activity marker (7-ethoxyresorufin O-deethylase) was inducible in the placentas by maternal cigarette smoking. Thus, the regulatory system of placental CYP1A1, mediated by the Ah-receptor, appears to be developed as early as the first trimester of pregnancy. Three immunoreactive bands from placental microsomes were detected by an antihuman CYP3A4 antibody, but no functional activity of CYP3A enzymes could be detected. These results show that placental tissue during the first trimester of pregnancy has the potential of expressing several CYP genes, and forms a basis for subsequent analysis of these forms at the protein and functional level.
对人类孕早期胎盘进行了外源代谢细胞色素P450(CYP)基因表达的筛查。通过逆转录聚合酶链反应(RT-PCR)在至少部分所研究的六个胎盘样本中鉴定出了CYP1A1、CYP1A2、CYP2C、CYP2D6、CYP2E1、CYP2F1、CYP3A4、CYP3A5、CYP3A7和CYP4B1的mRNA。在所有样本中均未检测到CYP2A和CYP2B的信息。与肝脏或肺中的相应水平相比,所有这些CYP mRNA的水平都较低。催化活性标志物(7-乙氧基试卤灵O-脱乙基酶)可因孕妇吸烟而在胎盘中被诱导。因此,由芳烃受体介导的胎盘CYP1A1调节系统似乎早在妊娠早期就已发育。用抗人CYP3A4抗体检测到胎盘微粒体中有三条免疫反应带,但未检测到CYP3A酶的功能活性。这些结果表明,妊娠早期的胎盘组织具有表达多种CYP基因的潜力,并为后续在蛋白质和功能水平上分析这些形式奠定了基础。