3β-HSD I

3β-HSD I (HSD3B1) catalyzes oxidation and isomerization of Δ5-3β-hydroxysteroid precursors into Δ4-ketosteroids, supporting formation of active steroid hormones^[1]. Mechanistically, HSD3B1 contributes mainly to 3β-HSD activity in placenta and peripheral tissues, while HSD3B2 is predominantly expressed in adrenal gland, ovary, and testis^[1]. In disease models, HSD3B1 correlated with CYP11B2 mRNA and plasma aldosterone concentration in aldosterone-producing adenoma, despite lower expression than HSD3B2^[2]. HSD3B1 polymorphisms rs33937873 and rs6203 were associated with prostate cancer susceptibility, but not recurrence prediction^[3]. Compared with HSD3B2, HSD3B1 shows higher affinity for substrates, coenzymes, and inhibitors, with His156, Gln105, and Gln240 contributing to isoform-specific kinetics^[4]. For experimental applications, epostane and trilostane shifted HSD3B1 inhibition constants in structure-function studies, supporting inhibitor-based analysis of isoform-sensitive steroidogenesis^[4].