Isolation and characterization of a cDNA encoding mouse 3alpha-hydroxysteroid dehydrogenase: an androgen-inactivating enzyme selectively expressed in female tissues.
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.
Bellemare
Véronique
V
Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), 2705 Laurier Boulevard, Que., Canada G1V 4G2.
Labrie
Fernand
F
Luu-The
Van
V
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
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)