HSD3B1

HSD3B1, or hydroxy-delta-5-steroid dehydrogenase 3 beta-1, is a human gene that encodes the enzyme 3β-hydroxysteroid dehydrogenase type I. This enzyme is part of the steroidogenic pathway and plays a key role in converting Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids, a step required for the production of progesterone and downstream steroid hormones.

As one of two human 3β-HSD isoforms, HSD3B1 is distinguished from HSD3B2, which encodes the type II enzyme. HSD3B2 is primarily expressed in the adrenal cortex and gonads, whereas HSD3B1 is enriched in the placenta and in several other tissues, contributing to placental production of progesterone that supports pregnancy. Both isoforms belong to the short-chain dehydrogenase/reductase (SDR) family and use NAD+ as a cofactor.

Substrate examples for 3β-HSD include pregnenolone (to progesterone), 17-hydroxypregnenolone (to 17-hydroxyprogesterone), and dehydroepiandrosterone (to androstenedione). Through these reactions, HSD3B1 participates in the biosynthesis of all major classes of steroid hormones, linking cholesterol metabolism to hormones such as progesterone, glucocorticoids, mineralocorticoids, and androgens.

Genetic variations in HSD3B1 can influence placental steroid production and fetal development in rare cases. Mutations in the related HSD3B2 gene are more commonly associated with congenital adrenal hyperplasia, a disorder of steroidogenesis.