17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) (HSD17B2)

17-beta-hydroxysteroid dehydrogenase type 2 (17β-HSD2) is a membrane-bound enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family that plays a critical role in the local regulation of steroid hormone activity [1, 6]. It primarily functions as an oxidoreductase, catalyzing the conversion of potent 17β-hydroxysteroids, such as estradiol and testosterone, into their less active 17-keto forms, estrone and androstenedione, respectively [1, 11]. By inactivating these hormones, 17β-HSD2 protects tissues from excessive estrogenic or androgenic stimulation [12, 14]. The enzyme is widely expressed in tissues including the liver, intestines, endometrium, and bone, where it modulates the microenvironment's hormonal balance [1, 15]. In clinical contexts, 17β-HSD2 is a significant therapeutic target for osteoporosis, as its inhibition can locally increase estradiol and testosterone levels in bone to promote bone mineral density [8, 12, 16]. Conversely, its deficient expression in the endometrium is a hallmark of endometriosis, leading to an accumulation of estradiol that drives lesion growth [12, 17]. In oncology, 17β-HSD2 expression levels serve as prognostic biomarkers in breast, prostate, and lung cancers, where altered activity influences tumor progression and response to endocrine therapies [9, 18, 21]. Current drug development efforts focus on identifying selective, non-steroidal inhibitors that can provide bone-specific benefits while minimizing systemic side effects [16, 19, 31].

Other names

17-beta-HSD 220 alpha-hydroxysteroid dehydrogenaseE2DHEstradiol 17-beta-dehydrogenase 2Microsomal 17-beta-hydroxysteroid dehydrogenaseShort chain dehydrogenase/reductase family 9C member 2Testosterone 17-beta-dehydrogenaseHSD17SDR9C2

Inhibition of 17-beta-hydroxysteroid dehydrogenase type 2 prevents the oxidative inactivation of potent steroids like estradiol and testosterone, thereby increasing their local concentrations in target tissues such as bone to stimulate bone formation and inhibit resorption.