EXPRESSION OF MULTIPLE FORMS OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE IN THE MOUSE-LIVER DURING FETAL AND POSTNATAL-DEVELOPMENT

The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) is essenti al for the biosynthesis of all steroid hormones. To dare this laborato ry has isolated and characterized five distinct 3 beta HSD cDNAs in th e mouse (3 beta HSD I-V). The different isoforms Fall into two functio nally distinct groups. 3 beta HSD I and III function as dehydrogenase/ isomerases and 3 beta HSD IV and V function as 3-ketosteroid reductase s. Previously it was shown that the liver of the adult mouse expresses 3 beta HSD II, III and V, with 3 beta HSD III being the major isoform . This study examines the expression of the different forms of 3 beta HSD mRNAs and proteins in the livers of male and female mice during fe tal and postnatal development. 3 beta HSD I, which in the adult mouse is expressed only in the gonads and adrenal glands, is the major isofo rm expressed in both male and female livers during fetal development u ntil the first postnatal (pn) day after which time 3 beta HSD III beco mes the major isoform. Expression of 3 beta HSD I mRNA and protein com pletely ceases after day 20 pn. The expression of 3 beta HSD V is firs t detected at day 40 pn and is observed only in the male. Very low exp ression of 3 beta HSD II mRNA is detected throughout development. Prev ious characterization of enzymatic activity of the expressed proteins showed that 3 beta HSD I exhibits lower K-m values for the Delta(5)-3 beta-hydroxysteroids than 3 beta HSD III, indicating that 3 beta HSD I functions as a more efficient 3 beta-hydroxysteroid dehydrogenase/iso merase than 3 beta HSD III. The results of this study suggest that the liver may play an important role in the biosynthesis of steroid hormo nes during murine fetal development.