Isolation and characterization of a cDNA encoding mouse 3α-hydroxysteroid dehydrogenase: An androgen-inactivating enzyme selectively expressed in female tissues

3α-Hydroxysteroid dehydrogenase catalyzes the transformation of 3-ketosteroids into 3α-hydroxysteroids, thus playing an important role in androgen and progesterone metabolism. So far, mouse cDNA and gene encoding 3α-HSD has not been reported. In this report, we describe the isolation of a mouse 3α-HSD cDNA and the characterization of its substrate specificity and tissue distribution. Sequence analysis indicates that m3α-HSD shares 87% amino acid identity with rat 3α-HSD. Cells stably transfected with this enzyme catalyze the transformation of dihydrotestosterone (DHT), 5α-androstanedione (5α-dione) and dihydroprogesterone (DHP) into 5α-androstane-3α,17β-diol (3α-diol), androsterone (ADT) and 5α-pregnan-3α-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 m3α-HSD could play an important role in the female mouse physiology similar to that of type 1 5α-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.