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 journalArticle

Abstract

17β‐N, N‐diethylcarbamoyl‐4‐methyl‐4‐aza‐5α‐an‐drostan‐3‐one (4‐MA) inhibits 5α‐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 5α‐dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5?‐reduc‐tase 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. 1984 American Society of Andrology

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

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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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