THE MULTIPLE MURINE 3-BETA-HYDROXYSTEROID DEHYDROGENASE ISOFORMS - STRUCTURE, FUNCTION, AND TISSUE-SPECIFIC AND DEVELOPMENTALLY SPECIFIC EXPRESSION

The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) is essenti al for the biosynthesis of all active steroid hormones. To date five d istinct isoforms have been identified in the mouse. The different isof orms are indicated by roman numerals (I-V) in the chronological order in which they have been isolated. The different isoforms are expressed in a tissue- and developmentally specific manner and fall into two fu nctionally distinct groups. 3 beta-HSD I, II, and III function as NAD( +)-dependent dehydrogenase/isomerases, and IV and V function as NADPH- dependent 3-keto steroid reductases. These latter two isoforms, theref ore, are not involved in the biosynthesis of steroid hormones, but mos t likely in the inactivation of steroid hormones. In the adult mouse 3 beta-HSD I is expressed in the classical steroidogenic tissues, the a drenal glands and the gonads. 3 beta-HSD II and III are expressed in t he liver and kidney, with III being the major isoform expressed in the adult liver. 3 beta-HSD II and III are expressed in the liver and kid ney, with III being the major isoform expressed in the adult liver. 3 beta-HSD IV is expressed almost exclusively in the kidney of both sexe s, 3 beta-HSD I is the major or only isoform expressed at 13.5 days po stconception and remains the major isoform until the day of birth, aft er which 3 beta-HSD III becomes the major isoform. Expression of 3 bet a-HSD I in the liver decreases after birth and ceases by day 20 postna tally. Thus the liver expresses four distinct isoforms of 3 beta-HSD, I, II, III, and V, at different times during development. The mouse 3 beta-HSD genes, Hsd3b, have been mapped to a small region on mouse chr omosome 3. Analysis of two yeast artificial chromosome (YAC) libraries identified one clone that contains the entire Hsd3b locus within a 14 00-kb insert. Hybridization by Southern blot analysis of restriction-e nzyme-digested YAC DNA using an 18-base oligonucleotide that hybridize s without mismatch to all known Hsd3b sequences indicates that there a re a total of seven Hsd3b genes or pseudogenes in the mouse genome. Fu rther analysis of mouse genomic DNA by pulse field gel electrophoresis suggests that all of the HSd3b gene family is found within a 400-kb f ragment. (C) 1997 by Elvesier Science Inc.