Cloning of mouse 17beta-hydroxysteroid dehydrogenase type 2, and analysing expression of the mRNAs for types 1, 2, 3, 4 and 5 in mouse embryos and adult tissues.
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.
Mustonen
M V
MV
Biocenter Oulu and Department of Clinical Chemistry, University of Oulu, Kajaanintie 50, FIN-90220 Oulu, Finland.
Poutanen
M H
MH
Isomaa
V V
VV
Vihko
P T
PT
Vihko
R K
RK
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000201:enzymology* / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012727:Sex Characteristics; D013379:Substrate Specificity; D014158:Transcription, Genetic
D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases