Molecular Classification
Enzyme, Oxidoreductase
Disease Roles
Congenital adrenal hyperplasiaAdrenal insufficiencyDisrupted sexual development/maturation

3-beta-hydroxysteroid dehydrogenase Overview

3-beta-hydroxysteroid dehydrogenase (3β-HSD) is a crucial enzyme in steroid hormone biosynthesis. It catalyzes the oxidative conversion of Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids, an essential step for producing all classes of active steroid hormones, including progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens. There are two main human isoforms: HSD3B1 (expressed mainly in placenta and peripheral tissues) and HSD3B2 (predominantly expressed in adrenal gland and gonads). Mutations in HSD3B2 cause congenital adrenal hyperplasia due to impaired steroidogenesis.

Mechanism of Action

Inhibition of 3β-HSD activity, thereby blocking the production of steroid hormones such as progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens.

Biological Functions

Steroid hormone biosynthesis
Conversion of Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids
Steroid degradation
Regulation of plasma hormone levels

Disease Associations

Congenital adrenal hyperplasia
Adrenal insufficiency
Disrupted sexual development/maturation

Safety Considerations

  • Potential for disrupting the balance of multiple steroid hormones.
  • Side effects related to glucocorticoid and mineralocorticoid deficiency.
  • Effects on sexual development and reproduction.

Associated Biomarkers

Biomarker
Elevated ratios of precursor steroids (e.g., pregnenolone, 17α-hydroxypregnenolone, DHEA) due to blocked conversion steps