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

3 alpha-Hydroxysteroid dehydrogenase catalyzes the transformation of 3-ketosteroids into 3 alpha-hydroxysteroids, thus playing an important role in androgen and progesterone metabolism. So far, mouse cDNA and gene encoding 3 alpha-HSD has not been reported. In this report, we describe the isolation of a mouse 3 alpha-HSD cDNA and the characterization of its substrate specificity and tissue distribution. Sequence analysis indicates that m3 alpha-HSD shares 87% amino acid identity with rat 3 alpha-HSD. Cells stably transfected with this enzyme catalyze the transformation of dihydrotestosterone (DHT), 5 alpha-androstanedione (5 alpha-dione) and dihydropro-esterone (DHP) into 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol), androsterone (ADT) and 5 alpha-pregnan-3 alpha-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 m3 alpha-HSD could play an important role in the female mouse physiology similar to that of type I 5a-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. (c) 2005 Elsevier Ltd. All rights reserved.