Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Liver specific enzyme that acts as NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain (PubMed:14672942, PubMed:10998348, PubMed:7650035, PubMed:1530633, PubMed:11158055, PubMed:10634139, PubMed:19218247). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:14672942). Acts preferentially as a 3-alpha-hydroxysteroid dehydrogenase (HSD) with a subsidiary 3-beta-HSD activity (PubMed:14672942). Catalyzes efficiently the transformation of the potent androgen 5-alpha-dihydrotestosterone (5alpha-DHT or 17beta-hydroxy-5alpha-androstan-3-one) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:11158055, PubMed:10998348, PubMed:14672942). Catalyzes the reduction of estrone into 17beta-estradiol but with low efficiency (PubMed:14672942). Metabolizes a broad spectrum of natural and synthetic therapeutic steroid and plays an important role in metabolism of androgens, estrogens, progestereone and conjugated steroids (PubMed:10998348, PubMed:14672942, PubMed:19218247). Catalyzes the biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leading to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route (PubMed:2427522). a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) + NADPH a 3alpha-hydroxysteroid + NAD(+) = a 3-oxosteroid + H(+) + NADH 5alpha-androstane-3alpha,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + H(+) + NADPH 5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + H(+) + NADPH 5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-hydroxy-5alpha-androstan-3-one + H(+) + NADH 17beta-estradiol + NADP(+) = estrone + H(+) + NADPH 17beta-estradiol + NAD(+) = estrone + H(+) + NADH (20S)-hydroxypregn-4-en-3-one + NADP(+) = H(+) + NADPH + progesterone (20S)-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH + progesterone 3alpha-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-androstan-3,17-dione + H(+) + NADPH NADP(+) + testosterone = androst-4-ene-3,17-dione + H(+) + NADPH NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) + NADH 3alpha-hydroxy-5alpha-androstane 17-O-(beta-D-glucuronate) + NADP(+) = 5alpha-dihydrotestosterone 17-O-(beta-D-glucuronate) + H(+) + NADPH (3beta,5alpha,17beta)-3-hydroxy-androstan-17-yl sulfate + NADP(+) = 5alpha-dihydrotestosterone sulfate + H(+) + NADPH 5alpha-androstane-3alpha,17beta-diol + NAD(+) = 3alpha-hydroxy-5alpha-androstan-17-one + H(+) + NADH chlordecone alcohol + NADP(+) = chlordecone + H(+) + NADPH Inhibited by nonsteroidal the anti-inflammatory drugs (NSAID) flufenamic (PubMed:14672942). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942). kcat is 1.99 min(-1) for 17beta-hydroxy-5alpha-androstan-3-one reduction. kcat is 1.79 min(-1) for 5alpha-androstan-3,17-dione reduction. kcat is 2.1 min(-1) for 5alpha-androstane-3alpha,17beta-diol oxydation. kcat is 1.39.1 min(-1) for 3alpha-hydroxy-5alpha-androstan-17-one oxydation (PubMed:10998348). kcat is 2.1 min(-1) for 5alpha-androstane-3alpha,17beta-diol oxydation (PubMed:10998348). kcat is 3.07 min(-1) for 5alpha-dihydrotestosterone sulfate (PubMed:19218247). kcat is 3.28 min(-1) for 5alpha-dihydrotestosterone 17-O-(beta-D-glucuronate) (PubMed:19218247). Steroid metabolism. Monomer. Liver specific. The N-terminus is blocked. The allele with Cys-145/Val-311 shows a three- to five-fold decrease in catalytic efficiency for xenobiotic and steroidal substrates compared to the Ser-145/Leu-311 allele. The gene represented in this entry may act as a disease modifier. A splicing mutation resulting in loss of AKR1C4 exon 2 has been found in affected individuals carrying a causative mutation in AKR1C2 (PubMed:21802064). These patients manifest a more severe disease phenotype than individuals only carrying mutations in AKR1C2. Belongs to the aldo/keto reductase family. Truncated N-terminus.