Mustonen M V, Poutanen M H, Isomaa V V, Vihko P T, Vihko R K
Biocenter Oulu and Department of Clinical Chemistry, University of Oulu, Kajaanintie 50, FIN-90220 Oulu, Finland.
Biochem J. 1997 Jul 1;325 ( Pt 1)(Pt 1):199-205. doi: 10.1042/bj3250199.
17beta-Hydroxysteroid dehydrogenases (17HSDs) are responsible for the conversion of low-activity sex steroids to more potent forms, and vice versa. 17HSD activity is essential for the biosynthesis of sex steroids in the gonads, and it is also one of the key factors regulating the availability of active ligands for sex-steroid receptors in various extragonadal tissues. In this study, we have characterized mouse 17HSD type 2 cDNA, and analysed the relative expression of 17HSD types 1, 2, 3, 4 and 5 mRNAs in mouse embryos and adult male and female tissues. The cDNA characterized has a open reading frame of 1146 bp, and encodes a protein of 381 amino acids with a predicted molecular mass of 41837 kDa. Northern-blot analysis of adult mouse tissues revealed that, of the different 17HSDs, the type 2 enzyme is most abundantly expressed. High expression of the enzyme, which oxidizes both testosterone and oestradiol, in several large organs of both sexes indicates that it is the isoform having the most substantial role in the metabolism of sex steroids. Interestingly, four of the five 17HSD enzymes were also detected by Northern blots of whole mouse embryos, and each of the enzymes showed a unique pattern of expression. The oestradiol-synthesizing type 1 enzyme predominates in early days of development embryonic day 7, but after that the oxidative type 2 enzyme becomes the predominant form of all 17HSDs. The data therefore suggest that there is transient oestradiol production in the early days of embryonic development, after which inactivation of sex steroids predominates in the fetus and placenta.
17β-羟基类固醇脱氢酶（17HSDs）负责将低活性的性类固醇转化为活性更强的形式，反之亦然。17HSD活性对于性腺中性类固醇的生物合成至关重要，也是调节各种性腺外组织中性类固醇受体活性配体可用性的关键因素之一。在本研究中，我们对小鼠2型17HSD cDNA进行了表征，并分析了1型、2型、3型、4型和5型17HSD mRNA在小鼠胚胎以及成年雄性和雌性组织中的相对表达。所表征的cDNA具有1146 bp的开放阅读框，编码一个由381个氨基酸组成的蛋白质，预测分子量为41837 kDa。对成年小鼠组织的Northern印迹分析表明，在不同的17HSD中，2型酶的表达最为丰富。该酶对睾酮和雌二醇均有氧化作用，在两性的几个大器官中高表达，表明它是在性类固醇代谢中起最重要作用的同工型。有趣的是，通过对整个小鼠胚胎的Northern印迹也检测到了五种17HSD酶中的四种，并且每种酶都表现出独特的表达模式。在胚胎发育早期（胚胎第7天），合成雌二醇的1型酶占主导，但此后氧化型2型酶成为所有17HSD的主要形式。因此，数据表明在胚胎发育早期有短暂的雌二醇产生，在此之后性类固醇的失活在胎儿和胎盘中占主导。
