3-beta-hydroxy-delta-5-steroid dehydrogenase (3β-HSD) (3β-HSD)

3-beta-hydroxy-delta-5-steroid dehydrogenase (3β-HSD) is a critical bifunctional enzyme that catalyzes the oxidative conversion of Δ5-3β-hydroxysteroids into Δ4-3-ketosteroids [3, 4]. This process is an essential step in the biosynthesis of all major classes of steroid hormones, including progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens [7, 8]. In humans, the enzyme exists in two isoforms: Type 1 (HSD3B1), expressed in the placenta and peripheral tissues, and Type 2 (HSD3B2), predominantly found in the adrenal glands and gonads [4, 12]. Mutations in the HSD3B2 gene lead to a rare form of congenital adrenal hyperplasia characterized by impaired steroid production and salt-wasting [9, 15]. Conversely, overactivity or specific genetic variants of HSD3B1 are linked to the progression of castration-resistant prostate cancer by facilitating the local synthesis of dihydrotestosterone from adrenal precursors [11, 14]. Pharmacological inhibition of 3β-HSD, such as with trilostane, is used to treat conditions like Cushing's syndrome and is being explored as a strategy to overcome hormone-dependent cancer resistance [3, 11].

Other names

3-beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [1, 4]3-beta-hydroxy-5-ene steroid dehydrogenase [1, 3]Progesterone reductase [3, 4]Delta-5-3-ketosteroid isomerase [5, 8]Steroid delta-isomerase [5, 8]HSD3B1 [5, 12]HSD3B2 [4, 12]SDR11E1 [5]SDR11E2 [4]

Inhibition of 3-beta-hydroxy-delta-5-steroid dehydrogenase prevents the conversion of delta-5-steroid precursors (such as pregnenolone and dehydroepiandrosterone) into delta-4-ketosteroids (such as progesterone and androstenedione), thereby blocking the synthesis of downstream active steroid hormones including cortisol, aldosterone, and testosterone [3, 7, 10].