CLONING OF MOUSE 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2, AND ANALYZING EXPRESSION OF THE MESSENGER-RNAS FOR TYPE-1, TYPE-2, TYPE-3, TYPE-4 AND TYPE-5 IN MOUSE EMBRYOS AND ADULT TISSUES

17 beta-hydroxysteroid dehydrogenases (17HSDs) are responsible for the conversion of low-activity sex steroids to more potent forms, and vic e versa. 17HSD activity is essential for the biosynthesis of sex stero ids in the gonads, and it is also one of the key factors regulating th e 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 encod es a protein of 381 amino acids with a predicted molecular mass of 418 37 kDa. Northern-blot analysis of adult mouse tissues revealed that, o f 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 det ected by Northern blots of whole mouse embryos, and each of the enzyme s showed a unique pattern of expression. The oestradiol-synthesizing t ype 1 enzyme predominates in early days of development embryonic day 7 , but after that the oxidative type 2 enzyme becomes the predominant f orm of all 17HSDs. The data therefore suggest that there is transient oestradiol production in the early days of embryonic development, afte r which inactivation of sex steroids predominates in the fetus and pla centa.