Oxidative 3alpha-hydroxysteroid dehydrogenase activity of human type 10 17beta-hydroxysteroid dehydrogenase

J Steroid Biochem Mol Biol. 2003 Nov;87(2-3):191-8. doi: 10.1016/j.jsbmb.2003.07.007.


In vitro enzyme assays have demonstrated that human type 10 17beta-hydroxysteroid dehydrogenase (17beta-HSD10) catalyzes the oxidation of 5alpha-androstane-3alpha,17beta-diol (adiol), an almost inactive androgen, to dihydrotestosterone (DHT) rather than androsterone or androstanedione. To further investigate the role of this steroid-metabolizing enzyme in intact cells, we produced stable transfectants expressing 17beta-HSD10 or its catalytically inactive Y168F mutant in human embryonic kidney (HEK) 293 cells. It was found that DHT levels in HEK 293 cells expressing 17beta-HSD10, but not its catalytically inactive mutant, will dramatically increase if adiol is added to culture media. Moreover, certain malignant prostatic epithelial cells have more 17beta-HSD10 than normal controls, and can generate DHT, the most potent androgen, from adiol. This event might promote prostate cancer growth. Analysis of the 17beta-HSD10 sequence shows that this enzyme does not have any ER retention signal or transmembrane segments and has not originated by divergence from a retinol dehydrogenase. The data suggest that the unique mitochondrial location of this HSD [Eur. J. Biochem. 268 (2001) 4899] does not prevent it from oxidizing the 3alpha-hydroxyl group of a C19 sterol in living cells. The experimental results lead to the conclusion that mitochondrial 17beta-HSD10 plays a significant part in a non-classical androgen synthesis pathway along with microsomal retinol dehydrogenases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics
  • 17-Hydroxysteroid Dehydrogenases / metabolism*
  • 3-Hydroxyacyl CoA Dehydrogenases*
  • 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / metabolism*
  • Alcohol Oxidoreductases / metabolism
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Cell Line
  • Dihydrotestosterone / metabolism
  • Epithelial Cells / enzymology
  • Epithelial Cells / metabolism
  • Humans
  • Male
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Prostate / cytology
  • Prostate / enzymology
  • Prostate / metabolism
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Transfection


  • Recombinant Proteins
  • Dihydrotestosterone
  • 17-Hydroxysteroid Dehydrogenases
  • Alcohol Oxidoreductases
  • 3-Hydroxyacyl CoA Dehydrogenases
  • retinol dehydrogenase
  • HSD17B10 protein, human
  • Hsd17b10 protein, mouse
  • 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)