Human Aldo-Keto Reductase Family 1 Member C3 (AKR1C3) Protein

Background

AKR1C3, also known as 17β-hydroxysteroid dehydrogenase type 5, is a multifunctional enzyme involved in the metabolism of steroid hormones, prostaglandins, and xenobiotics. AKR1C3 converts androstenedione to testosterone and estrone to estradiol, playing a central role in androgen and estrogen biosynthesis. It also reduces prostaglandin D2 to PGF2α, influencing inflammation, immune responses, and cell proliferation. AKR1C3 is overexpressed in hormone-dependent cancers, such as prostate, breast, and endometrial cancers, where it promotes tumor growth by enhancing local androgen and estrogen production. Its ability to detoxify lipid peroxidation products like 4-HNE also confers resistance to oxidative stress and chemotherapy. AKR1C3 is emerging as a therapeutic target in cancer, particularly in castration-resistant prostate cancer, where it sustains androgen receptor signaling. In addition to cancer, AKR1C3 regulates neurosteroids and prostaglandin pathways, linking it to inflammation, neuroprotection, and metabolic diseases.