17β-HSD

17β-HSD (17β-Hydroxysteroid Dehydrogenases) is a class of NADPH/NAD+ dependent oxidoreductases that primarily catalyze the reversible conversion between the 17β-hydroxyl and ketone groups of steroid hormones, playing a crucial role in the synthesis, activation, and inactivation of steroids. The 17β-HSD family mainly belongs to the short-chain dehydrogenase/reductase (SDR) family, with the exception of 17β-HSD5 (AKR1C3), which belongs to the aldo-keto reductase (AKR) family. To date, 14 different mammalian 17β-HSDs have been identified, of which 12 are expressed in human tissues, exhibiting diverse tissue distributions, subcellular localizations, and catalytic preferences (oxidation or reduction).
17β-HSD1 primarily catalyzes the conversion of estrone (E1) to estradiol (E2) and is associated with breast cancer, prostate cancer, and endometriosis. 17β-HSD2 catalyzes the oxidation of E2 to E1, while also regulating the interconversion between androstenedione (A4) and testosterone (T), playing a role in osteoporosis. 17β-HSD3 promotes the conversion of A4 to T and is crucial for male sexual differentiation. 17β-HSD4 is involved in fatty acid β-oxidation and steroid hormone inactivation. Additionally, 17β-HSD5 participates in steroid hormone and prostaglandin synthesis, whereas 17β-HSD7 is involved in cholesterol and estrogen biosynthesis. 17β-HSD10 exhibits broad substrate specificity, contributing to the metabolism of fatty acids, bile acids, and neurosteroids, and has been implicated in Alzheimer's disease (AD). The development of selective inhibitors targeting specific 17β-HSD isoforms has become an important strategy in related disease research^[1].

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