3β-HSD I

3β-Hydroxysteroid dehydrogenase type I (3β-HSD1, HSD3B1) is a bifunctional oxidoreductase that catalyzes the conversion of Δ5-steroid precursors into Δ4-ketosteroids, an essential step in the biosynthesis of progesterone, androgens, and estrogens^[1][2]. HSD3B1 is predominantly expressed in the placenta and peripheral steroid-responsive tissues, where it supports local steroid hormone production and regulates intracrine steroid metabolism^[3][4]. Mechanistically, HSD3B1 converts dehydroepiandrosterone (DHEA) to androstenedione and contributes to downstream estradiol and testosterone synthesis, thereby influencing steroid-dependent cellular signaling pathways^[1][5]. In breast cancer models, HSD3B1 functions as a critical enzyme for DHEA-derived estrogen production, and selective inhibition of HSD3B1 has therefore been investigated as a strategy to reduce intratumoral estrogen synthesis^[5][6]. In inflammatory and cancer-associated cellular models, interleukin-4 (IL-4) markedly induces HSD3B1 expression through STAT6 and PI3K-AKT signaling pathways, linking immune regulation to local steroidogenesis^[7]. Compared with the closely related isoform HSD3B2, which is predominantly expressed in the adrenal gland, ovary, and testis and is required for systemic steroid hormone production, HSD3B1 primarily mediates steroid metabolism in peripheral tissues and the placenta^[3][4][8]. This tissue-specific distribution distinguishes HSD3B1 from HSD3B2 and supports the development of isoform-selective inhibitors for experimental studies and endocrine-related disease research^[5][6].

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