3-alpha-hydroxysteroid dehydrogenase (3α-HSD)

3-alpha-hydroxysteroid dehydrogenase is an enzyme of the aldo-keto reductase superfamily that catalyzes the reversible conversion of 3-ketosteroids to 3α-hydroxysteroids, modulating the biological activity of androgens, estrogens, and progestins[1][5][9]. The enzyme exists in multiple isoforms (notably AKR1C1, AKR1C2, AKR1C3, and AKR1C4 in humans), each displaying unique tissue distribution and substrate specificity. By altering the occupancy of steroid hormone receptors, 3α-HSDs are central to hormone-dependent cellular processes, regulation of metabolism, and pathological states such as cancer and endocrine disorders. Structure-function studies highlight a conserved catalytic mechanism and a central role in steroid hormone balance, making this enzyme family a potential target for selective chemical inhibition[1][3][5][9].

Other names

3α-HSDAKR1C1, AKR1C2, AKR1C3, AKR1C4 (human isoforms)3-hydroxysteroid dehydrogenase (sometimes less specific)Androsterone reductase (context-specific)Human chlordecone reductase (type 1 isoform)

Competitive inhibition of ketosteroid reduction/oxidation active site Alteration of receptor ligand availability (by changing steroid levels, affecting downstream hormone signaling)