17-beta-hydroxysteroid dehydrogenase (17beta-HSD)

17-beta-hydroxysteroid dehydrogenases (17beta-HSDs) are a group of oxidoreductase enzymes that play a pivotal role in the final steps of steroid hormone biosynthesis and metabolism. They primarily catalyze the interconversion between less active 17-ketosteroids and their highly active 17-beta-hydroxy counterparts, such as the conversion of estrone to estradiol or androstenedione to testosterone [2][5]. This function allows them to act as critical pre-receptor regulators, modulating the intracellular potency of estrogens and androgens in various tissues including the ovaries, testes, prostate, and breast [1][7]. Due to their role in regulating hormone levels, 17beta-HSDs are major therapeutic targets for hormone-dependent diseases. Overexpression of Type 1 (HSD17B1) is frequently observed in breast cancer and endometriosis, while Type 3 (HSD17B3) and Type 5 (AKR1C3) are linked to prostate cancer progression [3][6]. More recently, Type 13 (HSD17B13) has emerged as a promising target for metabolic liver diseases like NASH, and Type 10 (HSD17B10) has been implicated in the pathogenesis of Alzheimer's disease [8][10]. Pharmaceutical interventions typically focus on selective inhibitors designed to block the local production of active hormones, thereby minimizing the systemic side effects associated with broader endocrine therapies like aromatase inhibitors [12][13].

Other names

17-ketosteroid reductase17-KSRHSD17BHydroxysteroid (17-beta) dehydrogenase17-beta-hydroxysteroid oxidoreductase

17-beta-hydroxysteroid dehydrogenases act as pre-receptor molecular switches that regulate the local concentration of active steroid hormones by catalyzing the NAD(P)H-dependent reversible conversion of 17-ketosteroids (less active) to 17-beta-hydroxysteroids (highly active) [1][4]. By inhibiting specific isoforms, drugs can selectively reduce the activation of estrogens or androgens in target tissues without depleting systemic hormone levels [7][13].