Molecular cloning of mouse 17 beta-hydroxysteroid dehydrogenase type 1 and characterization of enzyme activity.
The biological activity of certain estrogens and androgens is modulated by enzymes called 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs), which catalyze the interconversion between less active 17-oxosteroid and more active 17 beta-hydroxysteroid forms. In the present report, we describe cloning of mouse 17 beta-HSD type-1 cDNA from an ovarian library generated from 4,4'-(1,2-diethyl-1,2-ethenediyl)bisphenol-(diethylstilbestrol)-tr eated mice, and characterization of the corresponding enzyme. The open reading frame of the mouse 17 beta-HSD type-1 cDNA encodes a peptide of 344 amino acid residues with a predicted molecular mass of 36785 Da. The mouse 17 beta-HSD type-1 enzyme shares 63% and 93% overall identity with human and rat 17 beta-HSD type-1 enzymes, respectively, and the most striking differences between the mouse and human type-1 enzymes are between the amino acid residues 197 and 230 and in the carboxy terminus of the enzymes. Similarly to the human 17 beta-HSD type-1 enzyme, the mouse type-1 enzyme primarily catalyzes reductive reactions from 17-oxo forms to 17 beta-hydroxy forms in intact cultured cells, but unlike the human type-1 enzyme, the mouse enzyme does not prefer phenolic over neutral substrates. Thus, mouse 17 beta-HSD type 1 catalyzes reduction of androst-4-ene-3,17-dione (androstenedione) to 17 beta-hydroxyandrost-4-en-3-one (testosterone) as efficiently as 3 beta-hydroxyestra-1,3,5(10)-trien-17-one (estrone) to estra-1,3,5(10)-triene-3 beta, 17 beta-diol (estradiol). 17 beta-HSD type 1 is predominantly expressed in mouse ovaries, in which it is located in granulosa cells.
Nokelainen
P
P
Biocenter Oulu, University of Oulu, Finland.
Puranen
T
T
Peltoketo
H
H
Orava
M
M
Vihko
P
P
Vihko
R
R
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010053:Ovary / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015067:17-Hydroxysteroid Dehydrogenases