In vitro effects of an aromatase inhibitor on 5 alpha-reductase activity in human hypertrophic prostatic tissue

J Clin Endocrinol Metab. 1986 Jul;63(1):269-71. doi: 10.1210/jcem-63-1-269.


To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT), 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstan-3 beta, 17 beta-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4-14C-T as substrate, in the presence of 4-OH-A (10(-8) to 10(-6) M); the amounts of the 5 alpha-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), a known inhibitor of the 5 alpha-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily. Both 4-OH-A and 4-MA induced significant and dose-related decreases in the formation of both DHT and the diols. The degree of inhibition induced by the different concentrations of 4-OH-A and 4-MA were 31, 41, 72% and 57, 87, 97%, respectively. The decreased formation of the diols was a consequence of the decreased availability of DHT (the immediate precursor of the diols) and was not due to direct effects of the inhibitors on the 3-hydroxysteroid dehydrogenases; both 4-OH-A and 4-MA were totally unable to modify the conversion of DHT to the diols, when 4-14C-DHT was used as substrate. Thus, 4-OH-A inhibits the process of 5 alpha-reduction of T in BPH tissue. This molecule might represent a potential new agent for the prevention and/or treatment of human BPH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Aged
  • Androstane-3,17-diol / biosynthesis
  • Androstenedione / analogs & derivatives*
  • Androstenedione / pharmacology
  • Aromatase Inhibitors*
  • Azasteroids / pharmacology
  • Dihydrotestosterone / analogs & derivatives
  • Dihydrotestosterone / metabolism
  • Dihydrotestosterone / pharmacology
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Prostatic Hyperplasia / enzymology*
  • Testosterone / metabolism


  • 5-alpha Reductase Inhibitors
  • Aromatase Inhibitors
  • Azasteroids
  • Dihydrotestosterone
  • Androstane-3,17-diol
  • Testosterone
  • Androstenedione
  • 17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one
  • formestane