In vivo assay for conversion of testosterone to dihydrotestosterone by rat prostatic steroid 5 alpha-reductase and comparison of two inhibitors

Prostate. 1991;19(1):63-72. doi: 10.1002/pros.2990190107.


An in vivo assay for steroid 5 alpha-reductase in rat ventral prostate has been developed and used to compare the inhibitory activity of N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and 6-methylene-4-pregnene-3,20-dione (LY207320). Immature rats (70-80 g) received test compounds 30 min prior to s.c. injection of [3H]-T. The rats were sacrificed 30 min later and the ventral prostates were analyzed for [3H]-T metabolites. Intraprostatic [3H]-T and [3H]-DHT reached peak levels within 5 min after injection of [3H]-T and declined to about 25% of peak levels after 2 hr. 4-MA was a very potent inhibitor of [3H]-DHT formation with an estimated IC50 of 0.2 mg/kg. LY207320, an inhibitor of 5 alpha-reductase in vitro, was weakly active in vivo and did not achieve greater than 45% inhibition at high doses (greater than 200 mg/kg, s.c.). Tissue uptake of [3H]-T was also inhibited by LY207320, which may contribute to its inhibitory activity on accessory sex organ growth in the rat.

Publication types

  • Comparative Study

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • 5-alpha Reductase Inhibitors*
  • Androgen Antagonists / pharmacology*
  • Animals
  • Azasteroids / pharmacology*
  • Chromatography, High Pressure Liquid
  • Dihydrotestosterone / analogs & derivatives*
  • Dihydrotestosterone / metabolism*
  • Dihydrotestosterone / pharmacology
  • Dose-Response Relationship, Drug
  • Male
  • Progesterone / analogs & derivatives*
  • Progesterone / pharmacology
  • Prostate / enzymology*
  • Rats
  • Rats, Inbred F344
  • Testosterone / metabolism*
  • Time Factors
  • Tritium


  • 5-alpha Reductase Inhibitors
  • Androgen Antagonists
  • Azasteroids
  • Dihydrotestosterone
  • Tritium
  • 6-methylene-4-pregnene-3,20-dione
  • Testosterone
  • Progesterone
  • 17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase