N. Nishi et al., Androgen-regulated expression of a novel member of the aldo-keto reductasesuperfamily in regrowing rat prostate, ENDOCRINOL, 141(9), 2000, pp. 3194-3199
The rat prostate is dependent on androgen for normal growth and differentia
tion. In addition, the organ undergoes rapid cell death upon withdrawal of
androgen on castration, and the atrophied tissue is capable of regrowth aft
er androgen replacement in adult animals. In our search for novel factor(s)
that participate in this androgen-induced proliferation of adult rat prost
ate cells, we have generated a complementary DNA (cDNA) library enriched in
cDNAs transiently up-regulated after androgen stimulation in castrated rat
ventral prostate using a PCR-based subtractive hybridization technique. Se
quence analysis of about one hundred clones in the library showed that appr
oximately 70% of them are identical or closely related to genes of known fu
nction, the remaining ones showing no or very low similarity to any genes c
haracterized previously. Among the former a new member of the rat aldo-keto
reductase superfamily that is closely related to aflatoxin, B-1 aldehyde r
eductase has been identified. The newly identified protein (androgen-induci
ble aldehyde reductase, AIAR) and rat aflatoxin B-1 aldehyde reductase (AFA
R) exhibit 80% amino acid sequence homology. The enzymatic activity toward
4-nitrobenzaldehyde of recombinant AIAR expressed in Escherichia coli was a
bout 16% of that of rat AFAR. Northern blot analysis revealed ALAR expressi
on in various adult rat tissues in addition to the ventral and dorsolateral
prostates, which differs from the highly restricted expression of AFAR in
the kidney and liver. The AIAR messenger RNA (mRNA) content of the ventral
prostate was low in normal and castrated rats, transiently increased after
androgen administration to castrated rats, attaining a peak 12-24 h after t
he treatment. Although the physiological substrate(s) of AIAR has not been
identified, the current results suggest that AIAR expression is associated
with some growth-related processes in regrowing rat prostate.