Ig. Abbaszade et al., THE MOUSE 3-BETA-HYDROXYSTEROID DEHYDROGENASE MULTIGENE FAMILY INCLUDES 2 FUNCTIONALLY DISTINCT GROUPS OF PROTEINS, Molecular endocrinology, 9(9), 1995, pp. 1214-1222
The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) plays an e
ssential role in the biosynthesis of all steroid hormones. We previous
ly reported the isolation, characterization, and tissue-specific expre
ssion of four distinct but highly homologous 3 beta HSD cDNAs (forms I
, II, III, and IV). Enzymatic characterization of three of these isofo
rms demonstrated that mouse 3 beta HSD I and III function as dehydroge
nase/isomerases, but 3 beta HSD IV functions exclusively as a 3-ketost
eroid reductase. We now report the isolation and characterization of a
n additional distinct mouse 3 beta HSD cDNA, 3 beta HSD V, which is ex
pressed in the liver of male mice beginning in late puberty. Similar t
o 3 beta HSD IV, 3 beta HSD V functions exclusively as a 3-ketosteroid
reductase converting an active androgen, dihydrotestosterone (DHT), i
nto an inactive androgen, 5 alpha-androstane-3 beta,17 beta-diol. Expr
essed 3 beta HSD V, however, exhibits a considerably lower apparent Mi
chaelis-Menten constant (K-m) value for DHT than 3 beta HSD IV (0.47 m
u M vs. 2.2 mu M, respectively). The complete predicted amino acid seq
uence of 3 beta HSD II is also reported. The predicted amino acid sequ
ence of mouse 3 beta HSD V reveals that this new form is more closely
related to the 3-ketosteroid reductases, mouse 3 beta HSD IV and rat I
II (93 and 84% identity, respectively), than to the other rodent isofo
rms that share less than 75% identity. The 3-ketosteroid reductases, m
ouse 3 beta HSD IV and V and rat III, not only differ from all of the
other characterized 3 beta HSD isoforms in their substrate specificity
but also in their cofactor specificity utilizing NADPH rather than NA
DH. The characterization of this fifth member of the mouse 3 beta HSD
multigene family, as well as the report of the complete coding region
for 3 beta HSD II, demonstrates that members of this highly homologous
gene family fall into two functionally distinct groups of enzymes. On
e group, as represented by 3 beta HSD I and III (and most likely II),
functions as dehydrogenase/isomerases and is essential for the biosynt
hesis of active steroid hormones. The other group, represented by 3 be
ta HSD IV and V, functions as 3-ketosteroid reductases and is most lik
ely involved in the inactivation of active steroid hormones such as DH
T.