Inhibition of 5a‐Reductase Activity and Alteration of Nuclear Testosterone: Dihydrotestosterone Ratio in Human Genital Skin Fibroblasts

GARY D. BERKOVITZ, TERRY R. BROWN, AND CLAUDE J. MIGEON

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

17 beta-N, N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) inhibits 5 alpha-reductase activity in cultured human genital skin fibroblasts. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated that 4-MA is a competitive inhibitor, with an apparent Ki of 15 nM. 4-MA had a very low binding affinity for the androgen receptor. When fibroblasts were incubated in the presence of testosterone (T) and 4-MA, nuclear uptake of 5 alpha-dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5 alpha-reductase activity. While the overall sum for the nuclear uptake of T and DHT diminished, the nuclear uptake of T increased. Biological androgen inactivity cannot be precluded on the basis of nuclear T plus DHT uptake.

Original languageEnglish (US)
Pages (from-to)171-175
Number of pages5
JournalJournal of Andrology
Volume5
Issue number3
DOIs
StatePublished - Jan 1 1984
Externally publishedYes

Keywords

  • 5?‐reductase
  • androgen receptor
  • enzyme inhibitor
  • fibroblast
  • nuclear uptake

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Reproductive Medicine
  • Endocrinology
  • Urology

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