Aldo-keto reductase family 1 member C3

AKR1C3 (Aldo-keto reductase family 1 member C3) is a cytosolic enzyme that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids with broad substrate specificity (UniProt: P42330). It functions in classical and alternative androgen biosynthetic pathways, converting Δ4-androstenedione to testosterone and androsterone to 5α-androstane-3α,17β-diol, and also acts as a prostaglandin F2α synthase and estrogen metabolism enzyme, converting estrone to 17β-estradiol.

AKR1C3 participates in steroid hormone metabolism and prostaglandin signaling pathways. The enzyme's broad catalytic repertoire encompasses reduction of glucocorticoids, mineralocorticoids, and xenobiotic carbonyl compounds. UniProt reports no primary disease association annotation for this protein.

AKR1C3 is elevated in Alzheimer's disease brain tissue. Analysis of human post-mortem AD brain compared to age-matched controls using TMT-labeled quantitative proteomics across four subcellular fractions detected significant upregulation, with a mean log2 fold-change of 1.80 (Chaparral AD proteomics). This upregulation may reflect altered steroid or prostaglandin metabolism in AD pathology, though functional consequences remain to be determined.