Target intelligence / Profile preview

17-beta-hydroxysteroid dehydrogenase type 3 (HSD17B3)

Target: HSD17B3
Molecular classification: Enzyme, Short-chain dehydrogenase/reductase family (SDR)

Overview

17-beta-hydroxysteroid dehydrogenase type 3 (HSD17B3) is a key enzyme predominantly expressed in testicular Leydig cells, catalyzing the final step in androgen biosynthesis—the conversion of androstenedione to testosterone. Mutations in the HSD17B3 gene cause impaired testosterone production, leading to disorders of sex development in genetic males, under-masculinization of external genitalia, and potential infertility. While alternative pathways and other isozymes can provide some compensation (notably in non-human species), HSD17B3 is the main enzyme for testicular testosterone synthesis in humans and plays a crucial role in male sexual differentiation and reproductive function.

Other names: 17β-Hydroxysteroid dehydrogenase 317β-HSD3HSD17B3EDH17B3SDR12C2Estradiol 17-beta-dehydrogenase 2Short chain dehydrogenase/reductase family 12C member 2Testicular 17-beta-hydroxysteroid dehydrogenaseTestosterone 17-beta-dehydrogenase 3Hydroxysteroid (17-beta) dehydrogenase 3

Mechanism of action

Inhibition of HSD17B3 reduces conversion of androstenedione to testosterone, leading to decreased androgen production.

Biological functions

Androgen biosynthesisSteroid metabolismConversion of androstenedione to testosterone

Disease associations

Disorders of sex development (DSD)Male pseudohermaphroditismInfertilityEndocrine disordersOther (potential link to hormone-related cancers, though not a primary cancer gene)

Safety considerations

Inhibition may cause undervirilization or ambiguous genitalia in malesPotential for altered estrogen/androgen balance leading to endocrine or reproductive abnormalities

Interacting drugs

There are no widely approved or classically used drugs directly targeting HSD17B3, but potential inhibitors are under preclinical investigation as part of androgen biosynthesis modulation for prostate cancer and other hormone-dependent conditions.

Biomarkers

Androstenedione/testosterone ratio (used diagnostically)HSD17B3 gene mutation/sequence analysis (used for diagnosis in DSD)

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