3β-HSD

3β-HSD (3β-Hydroxysteroid Dehydrogenase) is a key enzyme in the steroid hormone biosynthesis pathway, catalyzing the conversion of precursors such as pregnenolone and dehydroepiandrosterone (DHEA) into progesterone and androstenedione, which are further used to synthesize glucocorticoids, mineralocorticoids, androgens, and estrogens.
3β-HSD exists in multiple isoforms in both humans and mice. In humans, the main isoforms are HSD3B1 (placenta, skin, mammary gland) and HSD3B2 (adrenal glands, gonads), with HSD3B2 being essential for the biosynthesis of glucocorticoids, mineralocorticoids, and sex hormones. In mice, 3β-HSD I is predominantly expressed in the adrenal glands and gonads, playing a key role in steroidogenesis, whereas 3β-HSD VI is expressed in the decidua and trophoblast cells during early pregnancy, regulating progesterone synthesis and potentially supporting embryo survival through immune suppression.
3β-HSD plays a crucial role in steroid biosynthesis, placental function, sex hormone metabolism, and endocrine disorders. HSD3B2 mutations can cause congenital 3β-HSD deficiency, leading to adrenal insufficiency, abnormal sexual development, and electrolyte imbalance. Dysregulation of HSD3B1 and HSD3B2 activity can result in androgen excess, contributing to polycystic ovary syndrome (PCOS). Moreover, HSD3B1 dysfunction has been implicated in recurrent early pregnancy loss, while 3β-HSD V, primarily expressed in the male liver, may promote the progression of androgen-dependent prostate cancer when aberrantly expressed^[1].

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