title: Isolation and characterization of a cDNA encoding mouse 3alpha-hydroxysteroid dehydrogenase: an androgen-inactivating enzyme selectively expressed in female tissues.
abstract: 3alpha-Hydroxysteroid dehydrogenase catalyzes the transformation of 3-ketosteroids into 3alpha-hydroxysteroids, thus playing an important role in androgen and progesterone metabolism. So far, mouse cDNA and gene encoding 3alpha-HSD has not been reported. In this report, we describe the isolation of a mouse 3alpha-HSD cDNA and the characterization of its substrate specificity and tissue distribution. Sequence analysis indicates that m3alpha-HSD shares 87% amino acid identity with rat 3alpha-HSD. Cells stably transfected with this enzyme catalyze the transformation of dihydrotestosterone (DHT), 5alpha-androstanedione (5alpha-dione) and dihydroprogesterone (DHP) into 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), androsterone (ADT) and 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone), respectively. Quantification of mRNA expression levels of this enzyme was determined in male and female mouse sex-specific tissues using quantitative Realtime PCR. We show that this enzyme is mainly expressed in female-specific tissues while being almost absent from male-specific tissues. In the liver, the same expression level is seen in both male and female, while there is 6-fold higher expression level in female pituitary than in male. These results strongly suggest that m3alpha-HSD could play an important role in the female mouse physiology similar to that of type 1 5alpha-reductase with which it works in tandem. This role could be related to the inactivation of excess of androgen and progesterone that are more severely regulated than in man.
authors.affiliation: Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), 2705 Laurier Boulevard, Que., Canada G1V 4G2.
authors.forename: Véronique
authors.initials: V
authors.lastname: Bellemare
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: Van
authors.initials: V
authors.lastname: Luu-The
mesh_terms: D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D015113:Androstane-3,17-diol / Q000378:metabolism; D000738:Androsterone / Q000378:metabolism; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification*; D003900:Desoxycorticosterone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005836:Genitalia, Female / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008297:Male; D008321:Mammary Glands, Animal / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D004092:20-alpha-Dihydroprogesterone; D015113:Androstane-3,17-diol; D003900:Desoxycorticosterone; D000738:Androsterone; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)