3β-Hydroxysteroid dehydrogenase type 1 (3β-HSD1)

3β-Hydroxysteroid dehydrogenase type 1 (3β-HSD1) is an enzyme that catalyzes key steps in the biosynthesis of all classes of steroid hormones by converting Δ⁵-3β-hydroxysteroids (such as pregnenolone and dehydroepiandrosterone) to Δ⁴-3-ketosteroids (progesterone, androstenedione, and others)[1][2]. It is encoded by the HSD3B1 gene in humans and is primarily expressed in placenta, mammary tissue, breast tumors, and peripheral tissues[1][3][5]. This enzyme is a key therapeutic target in hormone-dependent cancers—especially breast and prostate cancer—since it enables local, intratumoral synthesis of active estrogens and androgens from adrenal precursors, which contributes to tumor growth and treatment resistance[2][6]. Clinically, inhibitors such as trilostane are used to block its activity in endocrine disorders (e.g., Cushing’s syndrome) and have implications for hormone-dependent tumor management. Polymorphisms in HSD3B1, such as the 1245C allele, are associated with enhanced enzyme stability and resistance to hormonal therapy in prostate cancer[6]. 3β-HSD1 is also involved in metabolic regulation, with some evidence implicating it in obesity and cardiovascular risk due to its effects on steroid and lipid metabolism[4].

Other names

3β-HSD type 1HSD3B1 (gene encoding human type 1 isoform)3β-Hydroxysteroid dehydrogenase/Δ⁵-⁴ isomerase type 1

Competitive inhibition of 3β-HSD1 impedes conversion of dehydroepiandrosterone (DHEA) to more potent steroids, reducing levels of active androgens and estrogens[2][4]. Inhibition affects steroid hormone–dependent tumor growth and can modulate response to endocrine and cytotoxic therapies[2][6].