Androgen-regulated expression of a novel member of the aldo-keto reductase superfamily in regrowing rat prostate.

Abstract

The rat prostate is dependent on androgen for normal growth and differentiation. In addition, the organ undergoes rapid cell death upon withdrawal of androgen on castration, and the atrophied tissue is capable of regrowth after androgen replacement in adult animals. In our search for novel factor(s) that participate in this androgen-induced proliferation of adult rat prostate 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. Sequence analysis of about one hundred clones in the library showed that approximately 70% of them are identical or closely related to genes of known function, the remaining ones showing no or very low similarity to any genes characterized previously. Among the former a new member of the rat aldo-keto reductase superfamily that is closely related to aflatoxin, B1 aldehyde reductase has been identified. The newly identified protein (androgen-inducible aldehyde reductase, AIAR) and rat aflatoxin B1 aldehyde reductase (AFAR) exhibit 80% amino acid sequence homology. The enzymatic activity toward 4-nitrobenzaldehyde of recombinant AIAR expressed in Escherichia coli was about 16% of that of rat AFAR. Northern blot analysis revealed AIAR expression 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 the 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.