3β-Hydroxysteroid dehydrogenase (3β-HSD)

3β-Hydroxysteroid dehydrogenase (3β-HSD) is a key enzyme in steroid hormone biosynthesis, essential for converting Δ5-3β-hydroxysteroids (such as pregnenolone and dehydroepiandrosterone) to their Δ4-3-keto derivatives (such as progesterone and androstenedione), a critical step in the formation of all major classes of steroid hormones including glucocorticoids, mineralocorticoids, androgens, and estrogens[2][4][6][8]. It is present in the adrenal cortex, testes, ovaries, placenta, and peripheral tissues, with tissue-specific isoforms (HSD3B1, HSD3B2 in humans)[2][8]. Mutations lead to congenital adrenal hyperplasia due to 3β-HSD deficiency, affecting steroid production and resulting in a range of endocrine and developmental disorders[6]. The enzyme is an established therapeutic target in endocrinology and oncology research and is subject to drug interactions, but clinically used highly selective inhibitors are limited[4][8].

Other names

3beta-hydroxysteroid dehydrogenase3-beta-hydroxysteroid dehydrogenaseΔ5-4 isomeraseHSD3B1 (type I isozyme, human)HSD3B2 (type II isozyme, human)

Inhibition of steroid biosynthesis by blocking conversion of Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids, thus reducing downstream steroid hormones[2][8] - Enzyme inhibition (competitive, noncompetitive, or irreversible, depending on the drug)